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Aims Interleukin (IL)-5 mediates the development of eosinophils (EOS) that are essential for tissue post-injury repair. It remains unknown whether IL-5 plays a role in heart repair after myocardial infarction (MI). This study aims to test whether IL-5-induced EOS population promotes the healing and repair process post-MI and to reveal the underlying mechanisms. Method and results MI was induced by permanent ligation of the left anterior descending coronary artery in wild-type C57BL/6 mice. Western blot and real-time polymerase chain reaction revealed elevated expression of IL-5 in the heart at 5 days post-MI. Immunohistostaining indicated that IL-5 was secreted mainly from macrophages and type 2 innate lymphoid cells in the setting of experimental MI. External supply of recombinant mouse IL-5 (20 min, 1 day, and 2 days after MI surgery) reduced the infarct size and increased ejection fraction and angiogenesis in the border zone. A significant expansion of EOS was detected in both the peripheral blood and infarcted myocardium after IL-5 administration. Pharmacological depletion of EOS by TRFK5 pretreatment muted the beneficial effects of IL-5 in MI mice. Mechanistic studies demonstrated that IL-5 increased the accumulation of CD206+ macrophages in infarcted myocardium at 7 days post-MI. In vitro co-culture experiments showed that EOS shifted bone marrow-derived macrophage polarization towards the CD206+ phenotypes. This activity of EOS was abolished by IL-4 neutralizing antibody, but not IL-10 or IL-13 neutralization. Western blot analyses demonstrated that EOS promoted the macrophage downstream signal transducer and activator of transcription 6 (STAT6) phosphorylation. Conclusion IL-5 facilitates the recovery of cardiac dysfunction post-MI by promoting EOS accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis. Translational perspective Accumulating evidence suggests that modulation of innate and adaptive immune responses is a promising therapeutic strategy for myocardial infarction. In this study, we demonstrate that IL-5 exerts cardioprotective effects on infarcted myocardium by promoting eosinophil accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis. Hence, regulation of cardiac IL-5 level or eosinophil count may become a therapeutic approach for post-myocardial infarction cardiac repair in humans.

Rationale: The crosstalk between cardiac microvascular endothelial cells (CMECs) and cardiomyocytes (CMs) has emerged as a key component in the development of, and protection against, cardiac diseases. For example, activation of endothelial nitric oxide synthase (eNOS) in CMECs, by therapeutic strategies such as ischemic preconditioning, plays a critical role in the protection against myocardial ischemia/reperfusion (I/R) injury. However, much less is known about the signals produced by CMs that are able to regulate CMEC biology. Here we uncovered one such mechanism using Tongxinluo (TXL), a traditional Chinese medicine, that alleviates myocardial ischemia/reperfusion (I/R) injury by activating CMEC eNOS. The aim of our study is to identify the signals produced by CMs that can regulate CMEC biology during I/R. Methods: Ex vivo, in vivo, and in vitro settings of ischemia-reperfusion were used in our study, with the protective signaling pathways activated in CMECs identified using genetic inhibition (p70s6k1 siRNA, miR-145-5p mimics, etc.), chemical inhibitors (the eNOS inhibitor, L-NNA, and the small extracellular vesicles (sEVs) inhibitor, GW4869) and Western blot analyses. TritonX-100 at a dose of 0.125% was utilized to inactivate the eNOS activity in endothelium to investigate the role of CMEC-derived eNOS in TXL-induced cardioprotection. Results: We found that while CMEC-derived eNOS activity was required for the cardioprotection of TXL, activation of eNOS in CMECs by TXL did not occur directly. Instead, eNOS activation in CMECs required a crosstalk between CMs and CMECs through the uptake of CM-derived sEVs. We further demonstrate that TXL induced CM-sEVs contain increased levels of Long Intergenic Non-Protein Coding RNA, Regulator Of Reprogramming (Linc-ROR). Upon uptake into CMECs, linc-ROR downregulates its target miR-145-5p leading to activation of the eNOS pathway by facilitating the expression of p70s6k1 in these cells. The activation of CMEC-derived eNOS works to increase survival in both the CMECs and the CMs themselves. Conclusions: These data uncover a mechanism by which the crosstalk between CMs and CMECs leads to the increased survival of the heart after I/R injury and point to a new therapeutic target for the blunting of myocardial I/R injury.

Objective: We assessed the correlation between lactate dehydrogenase(LDH) to phosphate ratio and the prognosis of microsurgically clipping for ruptured intracranial aneurysm (rIA) in this study, to test the hypothesis that serum LDH to phosphate ratio could be a predictor for the outcome of microsurgically clipping for rIA. Methods: The rIA patients between 2012 and 2018 were retrospectively collected. Age, sex, Hunt-Hess(H-H) grade, Fisher grade, smoking, drink, medical history, aneurysm location, hydrocephalus, laboratory data including serum LDH, phosphate and LDH to phosphate ratio, related complication and the outcomes in 3 months were recorded. Results: A total of 1608 rIA patients in our institution were collected, and 856 patients treated by microsurgical clipping were enrolled. A significantly higher LDH- phosphate ratio on admission was observed in patients with poor outcome at 3 months (median±SD, 200.175±107.290 for mRS 0–2 vs 323.826±219.075 for mRS score 3–6; P Conclusions: LDH to phosphate ratio was a potential biomarker and could predict the unfavorable outcome of microsurgically clipping for rIA in 3 months. However, the detailed mechanism remain unclear and the conclusion needs be further confirmed by large-scale randomized clinical trials.

Background: The relationship between serum phosphate ion (sPi) and the occurrence of acute hydrocephalus (aHCP) in aneurysmal subarachnoid hemorrhage (aSAH) remains largely unknown and controversial. The primary aim of this study was to evaluate the association between sPi on admission and aHCP following aSAH. Methods: A prospective study was conducted on six hundred thirty-five patients over the age of 19 years diagnosed with aSAH in our institution from January 21, 2012, to December 30, 2019. Data on clinical characteristics, laboratory parameters, treatments, and outcomes were collected and analyzed. The association between lower sPi levels and aHCP was assessed in univariate and multivariate analyses. Propensity-score matching (PSM) analyses were adopted to reduce the baseline differences between the non-HCP group and HCP group. Results: The overall incidence of aHCP following aSAH was 19.37% (123/512). Lower sPi levels were detected in patients with aHCP compared with those without [0.86(0.67-1.06) mmol/L vs. 1.04(0.84-1.21)] mmol/L in the univariate analysis. In the multivariate analysis, lower sPi, high modified Fisher (mFisher) grade, and high Hunt-Hess grade were associated with aHCP [odds ratios (OR) 1.729, 95% CI 1.139–2.623, P=0.01; mFisher OR 0.097,95%CI 0.055-0.172, pConclusion: Lower sPi levels at admission were observed in patients with unfavorable outcomes. Lower sPi levels were associated with aHCP and poor prognosis, and the model constructed by sPi levels, Hunt-Hess grade, and mFisher grade significantly improves the prediction of aHCP after aSAH.

Our previous studies showed that the combination of atorvastatin (ATV) and single injection of ATV-pretreated mesenchymal stem cells (MSCs) (ATV-MSCs) at 1 week post-acute myocardial infarction (AMI) promoted MSC recruitment and survival. This study aimed to investigate whether the combinatorial therapy of intensive ATV with multiple injections of ATV-MSCs has greater efficacy at different stages to better define the optimal strategy for MSC therapy in AMI. In order to determine the optimal time window for MSC treatment, we first assessed stromal cell-derived factor-1 (SDF-1) dynamic expression and inflammation. Next, we compared MSC recruitment and differentiation, cardiac function, infarct size, and angiogenesis among animal groups with single, dual, and triple injections of ATV-MSCs at early (Early1, Early2, Early3), mid-term (Mid1, Mid2, Mid3), and late (Late1, Late2, Late3) stages. Compared with AMI control, intensive ATV significantly augmented SDF-1 expression 1.5∼2.6-fold in peri-infarcted region with inhibited inflammation. ATV-MSCs implantation with ATV administration further enhanced MSC recruitment rate by 3.9%∼24.0%, improved left ventricular ejection fraction (LVEF) by 2.0%∼16.2%, and reduced infarct size in all groups 6 weeks post-AMI with most prominent improvement in mid groups and still effective in late groups. Mechanistically, ATV-MSCs remarkably suppressed inflammation and apoptosis while increasing angiogenesis. Furthermore, triple injections of ATV-MSCs were much more effective than single administration during early and mid-term stages of AMI with the best effects in Mid3 group. We conclude that the optimal strategy is multiple injections of ATV-MSCs combined with intensive ATV administration at mid-term stage of AMI. The translational potential of this strategy is clinically promising. Stem Cells Translational Medicine 2019;8:1068–1083

The aim of the study is to investigate the value of serum iron and hemoglobin levels for predicting acute seizures following aneurysmal subarachnoid hemorrhage (aSAH). Clinical and laboratorial data from patients with ruptured intracranial aneurysms were collected in the retrospective study. Age, sex, symptom onset, history of diabetes and hypertension, history of coronary artery disease, temperature, Hunt–Hess grade, Fisher grade, aneurysm location, hemoglobin, serum potassium, sodium, calcium, phosphorus, and iron were collected. Acute seizures were determined as seizures within 1 week following aSAH. Propensity score matching (PSM) analyses were performed to correct imbalances in patient characteristics between seizure and non-seizure groups. A total of 760 patients were included. Incidence of acute seizures following aSAH was 6.4%. In the univariate analysis, significant differences were detected in age, admission Hunt–Hess grade, Fisher grade, hemoglobin, serum sodium, and serum iron between seizure and non-seizure groups. In multivariate logistic regression model, lower serum iron was considered as a risk factor for acute seizures (OR 0.182, 95% CI 0.084–0.393, p = 0.000), as well as lower hemoglobin (OR 0.977, 95% CI 0.962–0.993, p = 0.004) and higher serum sodium (OR 1.072, 95% CI 1.003–1.145, p = 0.039). After PSM, there were no significant differences in age, admission Hunt–Hess grade, Fisher grade, and serum sodium between seizure and non-seizure groups. The matched seizure group had lower serum iron and hemoglobin levels compared with the matched non-seizure group (p

Objective We tested the hypothesis that low serum iron levels are associated with acute hydrocephalus following aneurysmal subarachnoid hemorrhage (aSAH). Methods Patients presenting with ruptured intracranial aneurysms were enrolled in the prospective observational study. Age, sex, history of diabetes, hypertension and hyperlipidemia, symptom onset, Fisher grade, Hunt-Hess grade, aneurysm location, hemoglobin, and serum iron were collected. Acute hydrocephalus was determined within 72 hours after subarachnoid hemorrhage. A propensity-score matching analysis was performed to correct imbalances in patient characteristics between hydrocephalus and non-hydrocephalus groups. Results A total of 535 patients were included. Incidence of acute hydrocephalus was 20.0%. In multivariate logistic regression analysis, lower serum iron was considered as a risk factor of acute hydrocephalus, as well as delayed ischemic neurologic deficit and lower hemoglobin (P = 0.000). After propensity-score matching, lower serum iron was considered as an independent risk factor for acute hydrocephalus, whereas hemoglobin and delayed ischemic neurologic deficit were not. The matched hydrocephalus group had lower serum iron comparing with the matched non-hydrocephalus group (10.26 ± 5.33 mmol/L vs. 13.44 ± 5.18 mmol/L; P = 0.000). The optimal cut-off value for serum iron levels as a predictor for acute hydrocephalus in patients with aSAH was determined as 13.1 mmol/L in the receiver operating characteristic curve. Furthermore, lower serum iron levels (odds ratio 0.305; 95% confidence interval, 0.178–0.524; P = 0.000) and acute hydrocephalus (odds ratio 0.372; 95% confidence interval, 0.202–0.684; P = 0.001) were predictors of poor outcome, as well as higher Hunt-Hess grade and Fisher grade. Conclusions Lower serum iron levels after aSAH was a predictor of acute hydrocephalus and unfavorable outcome.

Background Medication errors (MEs) represent a significant burden to healthcare system and the frequency of potentially harmful MEs was found to be three times higher in paediatric population when compared to adults1. Objectives This review aims to analyse MEs to improve medication safety and compare the frequency of MEs compared to the previous audit cycle. Methods This is a retrospective analysis of medication errors in paediatric ward and neonatal unit utilising critical incident reporting forms (Datix) that were submitted from October 2018 to September 2019. These reports were obtained through the clinical audit department and patients‘ case notes were examined to review attributes of error. Results There were 38 incidents over the period of review (3.2 errors per month), demonstrating an improvement from the last audit cycle (4.5 errors per month). A large percentage (68%) of errors originated from paediatric ward and most of the errors were attributable to prescription errors. Doctors of all grades were identified to commit errors in prescription. Administration issues were the second most common cause for errors. Neither of these errors resulted in mortality and morbidity although some patients required additional monitoring as a consequence. Conclusions It is important to note that while errors were reducing in frequency, these errors could still potentially cause harm if they were not being addressed. Our trust is currently in the process of rolling out electronic prescribing and administration of medications to reduce medication errors and improve patient care. Another audit will be planned after the implementation of electronic system to review its usage to improve medication safety.

Percutaneous Endoscopic Gastrostomy (PEG) is increasingly being used in the pediatric population. We report a case of a 5-year-old boy who is fully PEG-fed that presented with a 2-day history of vomiting and diarrhea. His vomiting resolved however, the diarrhea remained persistent and watery with occasional undigested milk. His blood and stool investigation results were unremarkable however contrast study through the gastrostomy revealed migration of tube into the transverse colon. Laparoscopy was then performed for fistula resection and a new gastrostomy tube was inserted. Gastrostomy tube migration in children is not well-documented and this complication should be thought about when pediatricians are presented with a case of refractory diarrhea in PEG-fed patients.

ObjectiveTo test whether intensive atorvastatin (ATV) increases the efficacy of transplantation with autologous bone marrow mononuclear cells (MNCs) in patients suffering from anterior ST-elevated myocardial infarction (STEMI).MethodsThis clinical trial was under a 2×2 factorial design, enrolling 100 STEMI patients, randomly into four groups of regular (RA) or intensive ATV (IA) with MNCs or placebo. The primary endpoint was the change of left ventricular ejection fraction (LVEF) at 1-year follow-up from baseline, primarily assessed by MRI. The secondary endpoints included other parameters of cardiac function, remodelling and regeneration determined by MRI, echocardiography, positron emission tomography (PET) and biomarkers.ResultsAll the STEMI patients with transplantation of MNCs showed significantly increased LVEF change values than those with placebo (p=0.01) with only in the IA+MNCs patients group demonstrating significantly elevation of LVEF than in the IA+placebo group (+12.6% (95%CI 10.4 to 19.3) vs +5.0% (95%CI 4.0 to 10.0), p=0.001), pointing to a better synergy between ATV and MNCs (p=0.019). PET analysis revealed significantly increased viable areas of myocardium (p=0.015), while the scar sizes (p=0.026) and blood aminoterminal pro-B-type natriuretic peptide (pConclusionsIntensive ATV treatment augments the therapeutic efficacy of MNCs in patients with anterior STEMI at the convalescent stage. The treatment with the protocol of intensive ATV and MNC combination offers a clinically essential approach for myocardial infarction.Trial registration numberNCT00979758.

Background There is associating with incidence of unfavorable outcomes compared to microsurgical clippings. We are in order to investigate the outcomes of microsurgical clipping for intracranial aneurysms and determine the ideal clipping methods for different aneurysm subtypes. Method Retrospectively analyzed the clinical characteristics and follow-up data (completely recorded) of 123 patients with 128 aneurysms were treated. 20 cases were treated as control group from October 2013 to December 2013. Since January 2014, aneurysms were classified base on the 20 cases of aneurysm imaging data. 103 patients were treated as experimental group, the classification of aneurysms previously proposed was used to estimate the way of surgery, and the guiding value of the genotype was verified according to the intraoperative findings. The proposed aneurysm classification is based on the virtual surface of the aneurysm and the parent artery, the aneurysm neck was classified as follows: subtype I, the curved surface of the neck is a single curved surface; subtype II, the neck is hyperboloid; subtype III, neck is a three-curved surface. Aneurysms were divided into further subtypes according to the ratio of the width of the aneurysm neck surface and the length of the artery circumference: subtype A, the ratio of the aneurysm neck surface to the parent artery was not more than 0.5; subtype B, more than 0.5. There are some clamping methods include simple, sliding, interlocking and hybrid. Results In the control group, patients did not undergo a suitable clipping scheme without classification of aneurysm neck (unclassed clipping). While causing the occurrence of occlusion adverse events, including neck residual, Tumor artery stenosis, electrophysiological changes, the lack of blood supply and so on. The experimental[page1image12073600]group was analyzed by using a predetermined clipping scheme (classed clipping), and the use of aneurysms clamps was approximately the same as expected. Compared the preoperative assessment with the actual situation, the consistency of the control group was 50% and the experimental group was 96%. Adverse events of classed clipping is 2%, another is 60%. There is a significant difference between the two groups (P

To investigate the value of 3-dimensional (3D)-printed models with pathologic entities in enhancing the learning curve of surgery of tuberculum sellae meningioma.We printed 4 models of tuberculum sellae meningiomas based on radiologic data using a 3D printer. Participants were allocated to the 3D group and the atlas group. In the 3D group, participants learned surgery with the assistance of 3D models. In the atlas group, participants used only 2-dimensional materials to assist their learning. All participants undertook a pre-test and post-test. The scores were used to identify the difference in learning efficiency between the 2 groups.A total of 42 new trainees were recruited, of whom 22 were in the 3D group and 20 in the atlas group. The baseline data were not significantly different. The difference of pre-test score was not significant, either. However, the post-test score was significantly greater in the 3D group (P = 0.005), and the change in score was also significantly greater in the 3D group (P0.001). In accordance with the objective test, the subjective survey through a questionnaire from participants in the 3D group showed that 3D models significantly promoted the learning curve of this kind of complex skull base surgery.3D-printed models can assist in improving the learning curve of surgery of tuberculum sellae meningiomas. It particularly aids in memorization and spatial construction, improves understanding of surgical view, and arouses interest on the part of the trainee. We recommend using it in the education of complex skull base surgery.

It is not fully established whether leukocyte can predict the poor outcome for ruptured cerebral aneurysms (CA) or not. Here, we retrospectively analyzed the clinical data of 428 patients with ruptured CA between 2010 and 2015. Patients’ demographic data, including gender, age, history of smoking, alcohol, hypertension, diabetes and hypercholesterolemia, Hunt-Hess and Fisher grade, occurrence of hydrocephalus, aneurysm location, time to surgery, delayed ischemic neurological deficit (DIND) and peak leukocyte of blood test from day 1 to 3 after aneurysmal rupture were recorded and analyzed. In the multivariable analysis model, gender, Fisher grade, time to surgery and hydrocephalus were not relevant to poor outcome. However, Hunt-Hess grade, DIND and preoperative leukocyte count (>13.84 × 109/L) were significantly associated with adverse outcome. The respective increased risks were 5.2- (OR 5.24, 95% CI 1.67–16.50, p = 0.005), 6.2-(OR 6.24, 95% CI 3.55–10.99, p 13.84 × 109/L) were independent risk factors for poor outcome of ruptured CA at 3 months. Higher leukocyte count is a convenient and useful marker to predict 3-month poor outcome for ruptured CA.

Aim: To determine the efficacy and safety of intracoronary infusion of autologous bone marrow mesenchymal stem cells (MSCINJ) in combination with intensive atorvastatin (ATV) treatment for patients with anterior ST-segment elevation myocardial infarction-elevation myocardial infarction. Patients & methods: The trial enrolls a total of 100 patients with anterior ST-elevation myocardial infarction. The subjects are randomly assigned (1:1:1:1) to receive routine ATV (20 mg/d) with placebo or MSCsINJ and intensive ATV (80 mg/d) with placebo or MSCsINJ. The primary end point is the absolute change of left ventricular ejection fraction within 12 months. The secondary end points include parameters in cardiac function, remodeling and regeneration, quality of life, biomarkers and clinical outcomes. Results & conclusion: The trial will implicate the essential of cardiac micro-environment improvement (‘fertilizing’) for cell-based therapy. Clinical Trial Registration: NCT03047772.

Background Bone marrow mesenchymal stem cells (MSCs) are among the most common cell types to be used and studied for cardiac regeneration. Low survival rate and difficult retention of delivered MSCs in infarcted heart remain as major challenges in the field. Co-delivery of stem cell-derived exosomes (Exo) is expected to improve the recruitment and survival of transplanted MSCs. Methods Exo was isolated from MSCs and delivered to an acute myocardial infarction (AMI) rat heart through intramyocardial injection with or without intravenous infusion of atrovastatin-pretreated MSCs on day 1, day 3, or day 7 after infarction. Echocardiography was performed to evaluate cardiac function. Histological analysis and ELISA test were performed to assess angiogenesis, SDF-1, and inflammatory factor expression in the infarct border zone. The anti-apoptosis effect of Exo on MSCs was evaluated using flow cytometry and Hoechst 33342 staining assay. Results We found that intramyocardial delivery of Exo followed by MSC transplantation (in brief, Exo+MSC treatment) into MI hearts further improved cardiac function, reduced infarct size, and increased neovascularization when compared to controls treated with Exo or MSCs alone. Of note, comparing the three co-transplanting groups, intramyocardially injecting Exo 30 min after AMI combined with MSCs transplantation at day 3 after AMI achieved the highest improvement in heart function. The observed enhanced heart function is likely due to an improved microenvironment via Exo injection, which is exemplified as reduced inflammatory responses and better MSC recruitment and retention. Furthermore, we demonstrated that pre-transplantation injection of Exo enhanced survival of MSCs and reduced their apoptosis both in vitro and in vivo. Conclusions Combinatorial delivery of exosomes and stem cells in a sequential manner effectively reduces scar size and restores heart function after AMI. This approach may represent as an alternative promising strategy for stem cell-based heart repair and therapy.

Background Various computed tomography (CT) appearances of cerebral venous sinus thrombosis (CVST) were associated with different prognosis and the patients with large intracranial hematoma will have adverse outcomes, but no in-depth study of non-contrast CT image appearances was carried out. We aimed to test the hypothesis that non-contrast CT image characteristics on admission are associated with and predict the outcome of CVST at 3 months. Methods Three hundred and six patients with CVST between 2008 and 2017 were collected. Age, sex, onset of CVST(acute, subacute, or chronic), etiology, clinical manifestations, midline shift, occluded venous sinus, location of infarction, non-contrast CT image characteristics, and the 3-month outcome were recorded. In addition, we established a non-contrast CT image-based classification and grading system to test the hypothesis; the CVST patients were classified into four grades (namely non-contrast CT image-based classification): grade I, no obvious abnormality; grade II, simple vein infarction without hemorrhage or with subarachnoid hemorrhage; grade III, cerebral venous infarction with subarachnoid hemorrhage; and grade IV, cerebral vein infarction with hematoma. All enrolled patients had received subcutaneous injections of low molecular weight heparin subcutaneous injection for 14 days. Thereafter, oral anticoagulant therapy with warfarin was continued. Patients with epilepsy were given antiepileptic drugs, and patients with cerebral herniation received decompressive craniotomy. Results Our observational findings revealed that midline shift (> 5 mm), location of lesion (frontal lobe and temporal lobe), and cerebral venous infarction with subarachnoid or hematoma (grade III and IV) were associated with 3-month poor outcome (p 0.05). Conclusions Our findings suggested that non-contrast CT image characteristics on admission were associated with and predict the 3-month outcome of CVST. However, the ultimate conclusions need to be confirmed by a large sample of CVST patients at multiple institutions.

Objective The climatic characteristics of aneurysmal subarachnoid hemorrhage (aSAH) have been reported, but consensus has not yet been reached. It is of great significance to elucidate the relationships between meteorological variation and aSAH in regions with specific climate patterns. We analyzed the occurrence of aSAH in the capital city of Fujian Province, China, through a multicenter, 5-year study, and aimed to reveal the meteorological influences on aSAH in the coastal city of eastern Fujian under the subtropical marine monsoon condition. Methods A total of 2555 consecutive patients with aSAH in Fuzhou were collected using specialized stroke admission database from January 2013 to December 2017. Meteorological parameters including temperature, atmospheric pressure, and humidity were obtained from China Surface Meteorological Station during the same period. Poisson regression was used to explore the association between meteorological parameters and aSAH to calculate the incidence rate ratios (IRRs) with corresponding 95% confidence intervals (CIs). Generalized additive model analysis further revealed the nonlinear relationships between weather and aSAH. Results Daily minimum temperature (IRR 0.976, 95% CI 0.958–0.996) and maximum pressure (IRR 1.022, 95% CI 1.001–1.042) were independently correlated with the onset of aSAH. Low temperature (below 16°C) and excessive atmospheric pressure (above 1008 hPa) increased the risk of aSAH. In addition, March in spring and December in winter were the 2 ictus peaks in Fuzhou throughout the year. Conclusions Cold and excessive atmospheric pressure are triggers for the occurrence of aSAH; March in spring and December in winter are the predominant onset periods in Fuzhou.

Background A large craniotomy is usually the first choice for removal of traumatic acute subdural hematoma (TASDH). To date, few studies have reported that TASDH could be successfully treated by twist drill craniostomy (TDC) alone or combined with instillation of urokinase. We aimed to define the TDC for the elderly with TASDH and performed literature review. Case presentation A total of 7 TASDH patients, who were presented and treated by TDC in this retrospective study between January 2009 and May 2017, consisted of 5 men and 2 women, ranging in age from 65 to 89 (average, 78.9) years. The patients’ baseline characteristics, including age, sex, medical history, received ventriculoperitoneal shunt for hydrocephalus or not, reason for avoiding or refusing large craniotomy, preoperative Glasgow Coma Scale (GCS), suffered from cerebral herniation or not, the location of TASDH, imaging characteristics of TASDH in CT scan, injury/surgery time interval, midline shift, preoperative neurologic deficit, operation time, and infusions of urokinase or not, were collected. The postoperative GCS, postoperative neurologic deficit, rebleeding or not, intracranial infection, and modified Rankin Scale (mRS) at 6 months after surgery were analyzed to access the safety and efficacy of evacuation with TDC. The results showed that the mean time interval from injury to TDC was 68.6 min (30–120 min). The mean distance of midline shift was 14.6 mm (10–20 mm). The preoperative GCS in all patients ranged from 4 to 13(median, 9). The mean duration of the operation was 14.4 min (6–19 min). Postoperative CT scan showed that hematoma evacuation rate was more than 70% in all cases. There were no cases of acute rebleeding and intracranial infection after TDC. No cases presented with chronic SDH at the ipsilateral side within 6 months after being treated by TDC alone or combined with instillation of urokinase. Favorable outcomes were shown in all cases (mRS scores 0–2) at 6 months after surgery. Conclusions TASDH in the elderly could be safely and effectively treated by TDC alone or combined with instillation of urokinase, which was a possible alternative for the elderly.

Objective We tested the hypothesis that low hemoglobin levels are associated with acute seizures after aneurysmal subarachnoid hemorrhage (aSAH). Methods Patients with ruptured intracranial aneurysms were enrolled in the observational cohort study that prospectively collected age, sex, symptom onset, history of diabetes and hypertension, history of coronary artery disease, temperature, Hunt-Hess grade, Fisher grade, aneurysm location, hemoglobin, hematocrit, serum potassium, sodium, calcium, phosphorus, iron, and modified Rankin Scale. Acute seizures were determined as seizures within 1 week after aSAH. Results We included 554 patients with requisite data for analysis in the prospective study. Incidence of acute seizures following aSAH was 3.61%. In the univariate analysis, significant differences were detected in admission Hunt-Hess grade, Fisher grade, hemoglobin, and serum iron between epilepsy and nonepilepsy groups. Furthermore, acute seizures were associated with higher modified Rankin Scale score and poor outcome (P = 0.004). Serum hemoglobin levels were 114.30 ± 20.08 g/L in the epilepsy group, which were lower than those in the nonepilepsy group (128.64 ± 17.94 mmol/L, P = 0.001). Serum iron levels were 8.89 ± 5.03 g/L in the epilepsy group, which were also lower than those in the nonepilepsy group (13.71 ± 6.70 mmol/L, P = 0.002). The hemoglobin level was positively correlated with serum iron on admission (ρ = 0.321, P = 0.000). In the multivariate logistic regression model, lower hemoglobin was considered as an independent risk factor of acute seizures (odds ratio 4.286, 95% confidence interval 1.492–12.315, P = 0.007). The optimal cutoff value for hemoglobin level as a predictor for acute epilepsy after aSAH was determined as 119 g/L in the receiver operating characteristic curve (sensitivity was 75.00%, and specificity was 69.48%). Conclusions These data support the hypothesis that hemoglobin was inversely associated with acute seizures following aSAH.

Objective To determine whether extended lesionectomy is needed for patients with cerebral cavernous malformations presenting with epilepsy as compared with lesionectomy. Methods A literature search of PubMed, Embase, Web of Science, Clinical Trials and Cochrane Central Register of Controlled Trials was performed for pertinent English-language studies from 1967 to 2017. Eligible studies were selected according to uniform inclusion and exclusion criteria. Results Seven studies including 245 patients (107 receiving extended lesionectomy, 138 receiving lesionectomy) were selected. Meta-analysis and subgroup analyses were conducted to compare extended lesionectomy with lesionectomy. Pooled analysis demonstrated that seizure outcome was not statistically significantly improved in patients who underwent extended lesionectomy compared with lesionectomy (odds ratio = 0.77; 95% confidence interval, 0.39–1.51; P = 0.44; I2 = 15%). Conclusions Extended lesionectomy does not contribute to better seizure control for patients with cerebral cavernous malformations with epilepsy. Resection of the lesion and surrounding hemosiderin is sufficient for patients with cerebral cavernous malformations presenting with epilepsy.

Background We tested the hypothesis that high-density lipoprotein (HDL) is associated with intracranial aneurysm growth and rupture. Methods We used an observational cohort study design. Age, sex, admission systolic blood pressure (SBP), diabetes, hypertension, coronary artery disease, aneurysmal rupture, apolipoprotein (APO)-A1, APO-B, HDL, low-density lipoprotein, triglycerides, cholesterol, and aneurysm location and size were recorded. Aneurysms Results The data from 581 patients with intracranial aneurysms were analyzed. The predictive factors for small size of aneurysms were female sex (odds ratio [OR], 0.630; 95% confidence interval [CI], 0.428–0.927; P = 0.019) and higher HDL (OR, 0.327; 95% CI, 0.159–0.672; P = 0.0002). In the subgroup of male patients, lower HDL was the only risk factor for large size (P = 0.015). The predictors of aneurysmal rupture were small size (OR, 0.875; 95% CI, 0.842–0.910; P = 0.000), higher HDL (OR, 3.716; 95% CI, 1.623–8.509; P = 0.002), no coronary artery disease (OR, 4.736; 95% CI, 1.528–14.681; P = 0.007), lower APO-A1 (OR, 0.202; 95% CI, 0.064–0.641; P = 0.007), and higher admission SBP (OR, 1.024; 95% CI, 1.015–1.032; P = 0.000). An HDL/aneurysm size ratio >0.31 was associated with a 46.2-fold increased likelihood of aneurysmal rupture (OR, 46.214; 95% CI, 13.386–159.548; P = 0.002). Conclusions The HDL level was inversely associated with intracranial aneurysm growth, especially in men. Higher HDL levels and small aneurysm size contributed to a greater risk of aneurysmal rupture. An HDL/size ratio >0.31 was a valuable predictor of intracranial rupture.

Objective We tested the hypothesis that cerebellopontine angle (CPA) tumors are associated with a greater incidence of unruptured intracranial aneurysms (IAs). Methods Patients with intracranial tumors (ITs) undergoing computed tomography angiography and magnetic resonance imaging were enrolled in an observational cohort study that prospectively collected age, sex, hypertension, diabetes, cerebral arteriosclerosis, tumor type, tumor location, hydrocephalus, smoking, alcohol intake, CPA tumor size, cerebral aneurysms, and cerebral arteriosclerosis. Patients with the coexistence of IA and IT were classified as group II, whereas the others with IT as group I. Results We included 1218 patients with IT for analysis. The incidence of IA was 7.1% (86/1218). A total of 31% of patients with aneurysms had CPA tumors. In a multivariate logistic regression model, a greater incidence of IA was found in female patients (odds ratio [OR] 1.726, 95% confidence interval [CI] 1.050–2.836, P = 0.031) and in patients with CPA tumors (OR 3.002, 95% CI 1.822–4.947, P = 0.000) after adjustment for tumor type, cerebral arteriosclerosis, and age. In female patients, CPA tumors were a unique independent risk factor of a greater incidence of IA (OR 2.270, 95% CI 1.194–4.317, P = 0.012). Furthermore, cerebral arteriosclerosis was a unique independent risk factor of IA in patients with CPA tumors (OR 7.626, 95% CI 2.928–19.860, P = 0.000). Conclusions These data support the hypothesis that CPA tumors are associated with a greater incidence of unruptured IAs, especially in female patients. Cerebral arteriosclerosis contributed to elevated risk of IA in patients with CPA tumors.

We tested the hypothesis that ionized calcium levels at admission are associated with early hematoma expansion and functional outcome in patients with hypertensive intracerebral hemorrhage (HICH).Patients presenting with HICH were enrolled in the observational cohort study that prospectively collected age, sex, blood pressure, history of diabetes and smoking, time from symptom onset to initial computed tomography (CT), admission ionized calcium (iCa) and total calcium (tCa), coagulation function, Glasgow Coma Scale (GCS), and postoperative modified Rankin Scale score. Hematoma reconstruction on CT was performed to measure hematoma volumes. Hematoma expansion (HE) was defined as an increase of more than 30% or 6 mL in HICH volume. We performed univariate and multivariate analyses to assess for association of iCa level with early HE and functional outcome.We included 111 patients with HICH for analysis. Admission serum iCa was 1.10 mmol/L in patients with HE and 1.17 in patients without HE. Univariate analysis indicated significant difference of GCS, initial HICH volume, iCa, and tCa between the HE and non-HE groups (P0.05). Lower admission iCa (less than 1.12 mmol/L) was associated with HE (odds ratio [OR] 0.300, 95% confidence interval [CI] 0.095-0.951, P = 0.041) after adjustment for age, blood pressure, GCS score, time to initial CT scan, baseline HICH volume, prothrombin time, and tCa. Furthermore, predictive factors of poor outcome included iCa (OR 0.192, 95% CI 0.067-0.554, P = 0.002) and GCS score (OR 0.832, 95% CI 0.722-0.959, P = 0.011).These data support the hypothesis that lower ionized calcium is associated with early hematoma expansion and poor outcome in patients with hypertensive intracerebral hemorrhage.

Background Although coagulopathy have been proved to be a contributor to a poor outcome of aneurysmal subarachnoid hemorrhage (aSAH), the risk factors for triggering coagulation abnormalities have not been studied after aneurysm clipping. Methods We investigated risk factors of coagulopathy and analyzed the relationship between acute coagulopathy and outcome after aneurysm clipping. The clinical data of 137 patients with ruptured CA admitted to our institution was collected and retrospectively reviewed. Patient demographic data (age, sex), smoking, alcohol use, hypertension, diabetes, Hunt-Hess grade, Fisher grade, operation time, intraoperative total infusion volume, intraoperative blood loss, intraoperative transfusion, intraoperative hemostatic drug treatment, calcium reduction (preoperative free calcium concentration–postoperative free calcium concentration) were recorded. Coagulation was assessed within 24 h. Postoperative hemorrhage and infarction, deep venous thrombosis (DVT), and mortality were analyzed. Results Coagulopathy was detected in a total of 51 cases (group I), while not in 86 cases (group II). Univariable analysis demonstrated that age, smoking, alcohol use, intraoperative total infusion volume, intraoperative blood loss, intraoperative transfusion, and calcium reduction (≥ 1.2 mg/dl) were related to coagulopathy. Non-conditional logistic regression analysis showed that age [OR, 1.037 (95% CI, 1.001–1.074); p = 0.045] and calcium reduction (≥ 1.2 mg/dl) [OR, 5.509 (95% CI, 1.900–15.971); p = 0.002] were considered as the risk factors for coagulopathy. Hunt-Hess grade [OR, 2.641 (95% CI, 1.079–6.331); p = 0.033] and operation time [OR, 0.107 (95% CI, 1.012–0.928); p = 0.043] were considered as the risk factors for hypocoagulopathy. There were 6 cases (11.7%) with cerebral infarction in group I, while 6 cases (6.98%) in group II (χ 2 = 0.918, p = 0.338). There were 4 cases (7.84%) with rebleeding in group I, while 5 cases (5.81%) in group II (χ 2 = 0.215, p = 0.643). The mortality was 9.80% (5/51) in group I, while 1.16% (1/86) in group II (χ 2 = 5.708, p = 0.017). DVT was not detected in all cases. Conclusions In conclusion, age (≥ 65 years) and calcium reduction (≥ 1.2 mg/dl) were considered as the risk factors for coagulopathy and have been proved to be associated with higher mortality after aneurysm clipping.

Neuroglobin (Ngb) has a high affinity for oxygen and helps prevent hypoxic-ischemic brain damage. In this study we analyzed the relationship between Ngb levels and clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH).Serum Ngb levels were measured in 58 patients with aSAH and 27 control individuals using the enzyme-linked immunosorbent assay. To continuously assess aSAH, we measured serum Ngb levels on days 1, 2, 3, 5, and 7 after aSAH. Clinical data were collected using the Hunt and Hess Scale, the Glasgow Coma Scale (GCS), the World Federation of Neurological Surgeons (WFNS) Scale, and the modified Fisher Scale. Clinical outcomes included 6-month mortality and 6-month unfavorable outcomes (modified Rankin Scale (mRS) score of 3-6).Serum Ngb levels increased after aSAH, peaked on day 2, and then gradually decreased. Serum Ngb levels on admission were higher in the patient group than in the control group (7.67 ± 2.56 ng/mL vs. 6.45 ± 0.88 ng/mL, P0.05). Multivariate logistic regression analysis indicated that serum Ngb levels on day 2 after aSAH were independently related to 6-month mortality (odds ratio [OR] = 0.265, 95% confidence interval [CI] = 0.094-0.747, P0.05) and 6-month unfavorable outcomes (OR = 1.919, 95% CI = 1.158-3.180, P0.05), and receiver operating characteristic curve analysis showed that serum Ngb levels on day 2 predicted 6-month mortality and 6-month unfavorable outcomes, with areas under the curve of 0.893 (P0.05; 95% CI, 0.812-0.974) and 0.818 (P0.05; 95% CI, 0.691-0.954), respectively, based on the best thresholds.Serum Ngb levels on day 2 after aSAH were strongly associated with poor outcomes in aSAH, suggesting that Ngb may be a novel biomarker for predicting poor outcomes in aSAH.

Background and Aims: Tongxinluo (TXL) is a multifunctional traditional Chinese medicine that has been widely used to treat cardiovascular and cerebrovascular diseases. However, no studies have explored whether TXL can protect human cardiomyocytes (HCMs) from ischemia/reperfusion (I/R) injury. Reperfusion Injury Salvage Kinase (RISK) pathway activation was previously demonstrated to protect the hearts against I/R injury and it is generally activated via Akt or (and) Erk 1/2, and their common downstream protein, ribosomal protein S6 kinase (p70s6k). In addition, prior studies proved that TXL treatment of cells promoted secretion of VEGF, which could be stimulated by the increased phosphorylation of one p70s6k subtype, p70s6k1. Consequently, we hypothesized TXL could protect HCMs from I/R injury by activating p70s6k1 and investigated the underlying mechanism. Methods and Results: HCMs were exposed to hypoxia (18 h) and reoxygenation (2 h) (H/R), with or without TXL pretreatment. H/R reduced mitochondrial membrane potential, increased bax/bcl-2 ratios and cytochrome C levels and induced HCM apoptosis. TXL preconditioning reversed these H/R-induced changes in a dose-dependent manner and was most effective at 400 μg/mL. The anti-apoptotic effect of TXL was abrogated by rapamycin, an inhibitor of p70s6k. However, inhibitors of Erk1/2 (U0126) or Akt (LY294002) failed to inhibit the protective effect of TXL. TXL increased p70s6k1 expression and, thus, enhanced its phosphorylation. Furthermore, transfection of cardiomyocytes with siRNA to p70s6k1 abolished the protective effects of TXL. Among the micro-RNAs (miR-145-5p, miR-128-3p and miR-497-5p) previously reported to target p70s6k1, TXL downregulated miR-128-3p in HCMs during H/R, but had no effects on miR-145-5p and miR-497-5p. An in vivo study confirmed the role of the p70s6k1 pathway in the infarct-sparing effect of TXL, demonstrating that TXL decreased miR-128-3p levels in the rat myocardium during I/R. Transfection of HCMs with a hsa-miR-128-3p mimic eliminated the protective effects of TXL. Conclusions: The miR-128-3p/p70s6k1 signaling pathway is involved in protection by TXL against HCM apoptosis during H/R. Overexpression of p70s6k1 is, therefore, a potential new strategy for alleviating myocardial reperfusion injury.

To study the anatomy and clinical application of monolateral pterional keyhole approaches for treating bilateral cerebral aneurysms.Twelve formalin-fixed cadaveric heads underwent right pterional keyhole approaches for management of simulative contralateral aneurysms. The length of the contralateral middle cerebral artery (MCA), distal internal carotid artery (DICA), anterior cerebral artery, and ophthalmic segment of the internal carotid artery (OICA) was recorded. The operability of contralateral aneurysms was assessed using a modified numeric grading system. A total of 16 patients (12 patients with ruptured aneurysms) with bilateral cerebral aneurysms undergoing contralateral pterional keyhole approaches were included.The contralateral A1 segment of the anterior cerebral artery, proximal A2 segment, M1 segment of the MCA, DICA, and OICA was exposed via pterional keyhole approaches. An additional 2 mm of the OICA was exposed after incision of the falciform dural fold was completed. Contralateral aneurysms of the M1 segment (posterior), M2 segment, MCA bifurcation (inferior), A2 segment (lateral), DICA (posterior and lateral), and OICA (superior, inferior, and lateral) could not be fully exposed to perform simulated surgical clipping (operability rate75%). A total of 36 aneurysms underwent adequate surgical clipping via unilateral pterional keyhole approaches, whereas 1 aneurysm of the A3 segment did not.Contralateral aneurysms of the M1 segment (anterior, superior, and inferior), MCA bifurcation (superior and lateral), A1 segment, A2 segment (anterior, posterior, and medial), internal carotid artery bifurcation, DICA (anterior and medial), and OICA (medial) were fully exposed from different angles and surgical maneuvers were performed via pterional keyhole approaches, including in patients presenting with subarachnoid hemorrhage.

OBJECTIVEUsing intraoperative electrocorticography (ECoG) to identify epileptogenic areas and improve postoperative seizure control in patients with low-grade gliomas (LGGs) remains inconclusive. In this study the authors retrospectively report on a surgery strategy that is based on intraoperative ECoG monitoring.METHODSA total of 108 patients with LGGs presenting at the onset of refractory seizures were included. Patients were divided into 2 groups. In Group I, all patients underwent gross-total resection (GTR) combined with resection of epilepsy areas guided by intraoperative ECoG, while patients in Group II underwent only GTR. Tumor location, tumor side, tumor size, seizure-onset features, seizure frequency, seizure duration, preoperative antiepileptic drug therapy, intraoperative electrophysiological monitoring, postoperative Engel class, and histological tumor type were compared between the 2 groups.RESULTSUnivariate analysis demonstrated that tumor location and intraoperative ECoG monitoring correlated with seizure control. There were 30 temporal lobe tumors, 22 frontal lobe tumors, and 2 parietal lobe tumors in Group I, with 18, 24, and 12 tumors in those same lobes, respectively, in Group II (p < 0.05). In Group I, 74.07% of patients were completely seizure free (Engel Class I), while 38.89% in Group II (p < 0.05). In Group I, 96.30% of the patients achieved satisfactory postoperative seizure control (Engel Class I or II), compared with 77.78% in Group II (p < 0.05). Intraoperative ECoG monitoring indicated that in patients with temporal lobe tumors, most of the epileptic discharges (86.7%) were detected at the anterior part of the temporal lobe. In these patients with epilepsy discharges located at the anterior part of the temporal lobe, satisfactory postoperative seizure control (93.3%) was achieved after resection of the tumor and the anterior part of the temporal lobe.CONCLUSIONSIntraoperative ECoG monitoring provided the exact location of epileptogenic areas and significantly improved postoperative seizure control of LGGs. In patients with temporal lobe LGGs, resection of the anterior temporal lobe with epileptic discharges was sufficient to control seizures.

Objective To seek a cerebral perfusion pressure (CPP) threshold that can reduce the occurrence of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Methods We analyzed the clinical data of patients with the diagnosis of aSAH and underwent CPP monitoring in our department from February 2014 to December 2015. CPP was divided into four specified thresholds by every 10 mmHg increments, which were from 50 mmHg to 80 mmHg. The totally time ratio of CPP below each threshold was calculated. The correlation between the time ratio and DCI were analyzed using binary logistic regression. And receiver operating characteristic curve was performed to identify the cutoff time ratios at higher risk of DCI. Results Finally, 17 patients developed DCI from 60 patients who were recruited. The time ratios of CPP which was below 50 mmHg, 60 mmHg and 70 mmHg were found predictors of DCI by the binary logistic regression. The cutoff time ratios were 0.4% (AUC = 0.777), 7.0% (AUC = 0.702), 28.7% (AUC = 0.696) respectively. While at the level of 80 mmHg, the cutoff time ratio was 65% (AUC = 0.595). It was not related to DCI (P = 0.167). Patients suffered from DCI had a worse outcome than who did not at 3 month after aSAH (P = 0.018). Conclusion Time ratios at higher risk of DCI had a positive relationship with the CPP thresholds. Keeping CPP above 70 mmHg may be helpful to prevent DCI after aSAH, but it still needs further investigation.

Objective Cerebral ischemia is a major contributor to poor outcome after ruptured anterior communicating artery aneurysms (ACoAs), and is not well classified. In this article, we develop a classification and identify risk factors of cerebral ischemia after ruptured ACoAs. Methods Three hundred sixty patients with ruptured ACoAs undergoing microsurgical clipping were collected. Sex, age, smoking status, Hunt-Hess grade, Fisher grade, hospital stay, surgical timing, hypertension, diabetes, postoperative cerebral ischemia, and postoperative modified Rankin Scale score were collected. Postoperative ischemic changes are classified according to a novel grade (ischemic grade I–IV). Results Predictive factors of postoperative ischemia (grade I–IV) included sex (odds ratio [OR], 1.956; 95% confidence interval [CI], 1.262–3.032; P = 0.003) and Fisher grade (OR, 1.813; 95% CI, 1.144–2.871; P = 0.011). Male sex had a tendency to develop postoperative cerebral ischemia (61.3% in the ischemia group vs. 45.7% in the nonischemia group), while surgical timing did not. However, in patients with postoperative ischemia, early surgery within 3 days (OR, 3.334; 95% CI, 1.411–7.879; P = 0.006) and advanced age greater than 55 years (OR, 2.783; 95% CI, 1.214–6.382; P = 0.016) were risk factors for postoperative neurologic deficits (grade III–IV). Conclusions Male sex and higher Fisher grade predict postoperative ischemia (grade I–IV), whereas surgical timing does not. However, in patients with postoperative cerebral ischemia, early surgery within 3 days and age greater than 55 years can increase the frequency of postoperative neurological deficits (grade III–IV). Older male patients undergoing early microsurgery had a tendency to develop neurologic deficits.

Gliosarcoma cell line K308 was established from a primary tumor specimen removed from a 51-year-old male Han Chinese patient. Besides the typical characteristics of gliosarcoma cells, K308 cells express abundant glutaminase and can release large amount of glutamate. K308 exhibited cell-density-dependent expression of neuronal precursor markers, particularly nestin. At low density, the majority of K308 cells were nestin negative (approximately 70%) and nestin levels remained homogenous within each single-cell-derived colony when K308 proliferated. After reaching confluence, however, the majority of K308 cells turned nestin positive. These confluent K308 cells were also Sox2 positive and could form tumor spheres even in serum-containing media.

Glioma glutamate release has been shown to promote the growth of glioma cells and induce neuronal injuries from epilepsy to neuronal death. However, potential counteractions from normal astrocytes against glioma glutamate release have not been fully evaluated. In this study, we investigated the glutamate/glutamine cycling between glioma cells and astrocytes and their impact on neuronal function. Co-cultures of glioma cells with astrocytes (CGA) in direct contact were established under different mix ratio of astrocyte/glioma. Culture medium conditioned in these CGAs were sampled for HPLC measurement, for neuronal ratiometric calcium imaging, and for neuronal survival assay. We found: (1) High levels of glutaminase expression in glioma cells, but not in astrocytes, glutaminase enables glioma cells to release large amount of glutamate in the presence of glutamine. (2) Glutamate levels in CGAs were directly determined by the astrocyte/glioma ratios, indicating a balance between glioma glutamate release and astrocyte glutamate uptake. (3) Culture media from CGAs of higher glioma/astrocyte ratios induced stronger neuronal Ca2+ response and more severe neuronal death. (4) Co-culturing with astrocytes significantly reduced the growth rate of glioma cells. These results indicate that normal astrocytes in the brain play pivotal roles in glioma growth inhibition and in reducing neuronal injuries from glioma glutamate release. However, as tumor growth, the protective role of astrocytes gradually succumb to glioma cells.

Stem cell therapy is a promising approach to the treatment of ischemic heart disease via replenishing cell loss after myocardial infarction. Both preclinical studies and clinical trials have indicated that cardiac function improved consistently, but very modestly after cell-based therapy. This mainly attributed to low cell survival rate, engraftment and functional integration, which became the major challenges to regenerative medicine. In recent years, several new cell types have been developed to regenerate cardiomyocytes and novel delivery approaches helped to increase local cell retention. New strategies, such as cell pretreatment, gene-based therapy, tissue engineering, extracellular vesicles application and immunologic regulation, have surged and brought about improved cell survival and functional integration leading to better therapeutic effects after cell transplantation. In this review, we summarize these new strategies targeting at challenges of cardiac regenerative medicine and discuss recent evidences that may hint their effectiveness in the future clinical settings.

Background: The protection of endothelial cells (ECs) against reperfusion injury has received little attention. In this study, we used Tandem Mass Tag (TMT) labeling proteomics to investigate the modulated proteins in an in vitro model of cardiac microvascular endothelial cells (CMECs) subjected to ischemia/reperfusion (I/R) injury and their alteration by traditional Chinese medicine Tongxinluo (TXL). Methods: Human CMECs were subjected to 2 h of hypoxia followed by 2 h of reoxygenation with different concentrations of TXL Protein expression profiles of CMECs were determined using tandem mass spectrometry. We evaluated several proteins with altered expression in I/R injury and summarized some reported proteins related to I/R injury. Results: TXL dose-dependently decreased CMEC apoptosis, and the optimal concentration was 800 µg/mL. I/R significantly altered proteins in CMECs, and 30 different proteins were detected between a normal group and a hypoxia and serum deprivation group. In I/R injury, TXL treatment up-regulated 6 types of proteins including acyl-coenzyme A synthetase ACSM2B mitochondrial (ACSM2B), cyclin-dependent kinase inhibitor 1B (CDKN1B), heme oxygenase 1 (HMOX1), transcription factor SOX-17 (SOX17), sequestosome-1 isoform 1 (SQSTM1), and TBC1 domain family member 10B (TBC1D10B). Also, TXL down-regulated 5 proteins including angiopoietin-2 isoform c precursor (ANGPT2), cytochrome c oxidase assembly factor 5 (COA5), connective tissue growth factor precursor (CTGF), cathepsin L1 isoform 2 (CTSL), and eukaryotic elongation factor 2 kinase (LOC101930123). These types of proteins mainly had vital functions, including cell proliferation, stress response, and regulation of metabolic process. Conclusions: The study presented differential proteins upon I/R injury through a proteomic analysis. TXL modulated the expression of proteins in CMECs and has a protective role in response to I/R.

The development of three-dimensional (3D) printing technology provides a new method for surgical treatment, but currently there are few reports on its application in the treatment of aneurysm. The aim of the present study was to explore the materials and methods of fabricating 3D printed individual aneurysm model and its value in the treatment of intracranial aneurysm. Twenty-four patients with intracranial aneurysm diagnosed by CTA who had undergone operation in our hospital were analyzed retrospectively. CTA Data collected at the time of surgery was used for reconstruction. Soft Mimics 17.0 was used to reconstruct the thin layer CTA scan data into 3D image and the final data was sent to the 3D printer for fabricating the model. We compared the proposed 3D printed model-based preoperative plan and the actual approach used in the surgery based on CTA data to evaluate the value of the 3D printed model in preoperative planning, and picked out the materials which were more suitable for the clinic. Twenty-four aneurysm models with high degree of reality were fabricated successfully with 3D-printing technology. The patients’ blood vessels, skulls and aneurysms were printed into the reality model at a ratio of 1:1. It is reported that the soft material-based, 3D printed vascular and aneurysm model more closely resembled the characteristics of the real blood vessels, thus provides a better simulation compared to the plaster-based model. Compared with the original operation plan, 3D printed model could be used for pre-operative aneurysm clip selection, and provide more intuitive information in selection of operational approach. 3D printed model can be used as an operational physical model to design operative schemes, choose the best operative paths and select suitable aneurysm clips by its high simulation degree and individualized characteristics. The model is helpful for surgical planning, especially for the preoperative plan of treating refractory multiple aneurysms and giant aneurysms.

Supplemental Digital Content is available in the text, Poor-grade ruptured anterior circulation cerebral aneurysms are frequently associated with severe vasospasm and high morbidity rates despite recent remarkable advances in endovascular coiling. Here, we explored the feasibility of keyhole approach combined with external ventricular drainage for ruptured, poor-grade, anterior circulation cerebral aneurysms. We retrospectively assessed the records of 103 patients with ruptured, Hunt and Hess grade IV or V, anterior circulation cerebral aneurysms. The patients were divided into 2 groups (conservative group and surgical group). In surgical group, patients were divided into 2 subgroups according to surgical time (within 24 hours and at 24–48 hours). Clinical outcome was assessed at the 6-month follow-up and categorized according to modified Rankin Scale (mRS) score. Twenty percent of patients (9/44) in conservative group obtained good outcome, while 54% (32/54) in surgical group (P 0.05). Furthermore, 65% of patients (22/34) operated within 24 hours after onset of hemorrhage had a good outcome compared with 20% of patients (5/25) operated at 24 to 48 hours in surgical group (P

Brain retraction is required during many intracranial procedures to provide more working space. However, it is difficult to avoid brain retraction injury. Here, we report on retractorless surgery for anterior circulation aneurysms via a pterional keyhole approach. All patients undergoing a minimally invasive pterional keyhole approach within 3 days after hemorrhage by the same surgeon were included in the study. Patients were randomly assigned into group I (with the retractorless technique) and group II (with fixed retractors). Data on adequate clipping level, intraoperative ischemia induced by retraction, operation time, brain retraction injury, intraoperative blood loss, intraoperative aneurysm rupture, and modified Rankin Scale were collected for the 2 groups. A consecutive series of 47 patients (21 patients in group I, 26 patients in group II) successfully underwent a minimally invasive pterional keyhole approach. Statistical analysis revealed no significant between-group differences with regard to sex, age, Hunt-Hess grade, adequate clipping level, operation time, intraoperative blood loss, and aneurysm rupture (P > 0.05). However, no intraoperative ischemia was detected in group I, whereas 23.1% (6 of 26) of patients in group II had reversible ischemia. Furthermore, the proportion of brain retraction injuries in group I (5.3%) was lower than that in group II (34.6%). In addition, a better prognosis was obtained in patients who underwent retractorless surgery. With the careful and accurate use of a handheld suction device and operating instruments, the retractorless technique can replace fixed retraction, reduce brain retraction injury, and is applicable to surgeries on anterior circulation aneurysms via pterional keyhole approaches.

Aim Traditional craniotomies for treatment of the aneurysms at the A3 segment of anterior cerebral artery (A3As), such as frontal approach and interhemispheric approach, require pre-hairline incision and relatively long incision, extensive bone flap, inevitable supraorbital nerve injury, opening frontal sinus, and increased operative time. Here we reported anterior interhemispheric keyhole approach with minimally invasive advantages for treatment of A3As. Material and methods Thirteen A3As and one A1 aneurysm in thirteen patients were confirmed by computed tomographic angiography (CTA) and/or digital subtraction angiography (DSA). All patients underwent anterior interhemispheric keyhole approach with a hairline incision across the midline and a bone flap 3-4 cm in diameter, combined with external ventricular drainage, neuronavigation, intraoperative neurophysiological monitoring (IONM), and transcranial Doppler (TCD). Clinical characteristics and therapeutic results of the patients were analyzed, and the postoperative functional capacities of those patients were evaluated using Glasgow Outcome Scale (GOS) six months later. Results All aneurysms were successfully obliterated via the anterior interhemispheric keyhole approach combined with external ventricular drainage. Mean duration of surgery (from skin incision to wound closure) was 100 minutes with a range of 70 to 135 minutes. No severe interhemispheric keyhole approach related complications, postoperative infections, secondary intracranial haemorrhage, severe cerebral vasospasm, and aneurysmal neck remnants were detected. Median hospital stay after surgery was 9.0 days (range 8 to 11 days). And the postoperative functional capacities evaluated by GOS were normal six months later. Conclusion The anterior interhemispheric keyhole approach combined with external ventricular drainage is a safe, effective, and minimally invasive craniotomy technique for the treatment of A3 aneurysms.

Rationale:Intracranial ganglioneuroblastoma represents a rare subtype of primitive neuroectodermal tumor. Here, we report a hippocampal ganglioneuroblastoma and a literature review of cerebral anglioneuroblastoma is carried out.Patient concerns:We report a 16-year-old male patient presenting

Rationale There were a few case reports concerning epidermoid tumor coexisted with multiple cerebral aneurysms. Here, we present one case of coexistence of intracranial epidermoid tumor and multiple cerebral aneurysms and performed a literature review. Patient concerns A 42 years old male patient was admitted to our institution with complaints of headache and dizziness. Interventions The radiological examinations showed a hypointense lesion in the right parasellar and petrous apex region and an ipsilateral saccular aneurysm originated from the M2-M3 junction of the right middle cerebral artery (MCA) and a saccular aneurysm of the clinoid segment of right internal carotid artery (ICA). Interventions The patients underwent a right frontotemporal approach for removal of the epidermoid tumor and clipping of the MCA aneurysm in one stage. The aneurysm located at the clinoid segment of ICA was invisible and untreated during operation. Outcomes No postoperative complications were found in the patient. The patient's follow up after 5 years of surgical treatment was uneventful, and the untreated aneurysm remains stable. Lessons The coexistence of intracranial epidermoid tumor and cerebral aneurysm is a rare event. The secondly inflammation in cerebral arterial wall may be responsible for the aneurysm formation. Surgical treatment of the intracranial epidermoid tumor and cerebral aneurysm repair may be an optimal scheme in one stage.

Epidermal growth factor receptor (EGFR/HER1/c-ErbB1), is overexpressed in many solid cancers, such as epidermoid carcinomas, malignant gliomas, etc. EGFR plays roles in proliferation, invasion, angiogenesis and metastasis of malignant cancer cells and is the ideal antigen for clinical applications in cancer detection, imaging and therapy. Aptamers, the output of the systematic evolution of ligands by exponential enrichment (SELEX), are DNA/RNA oligonucleotides which can bind protein and other substances with specificity. RNA aptamers are undesirable due to their instability and high cost of production. Conversely, DNA aptamers have aroused researcher's attention because they are easily synthesized, stable, selective, have high binding affinity and are cost-effective to produce. In this study, we have successfully identified DNA aptamers with high binding affinity and selectivity to EGFR. The aptamer named TuTu22 with Kd 56±7.3nM was chosen from the identified DNA aptamers for further study. Flow cytometry analysis results indicated that the TuTu22 aptamer was able to specifically recognize a variety of cancer cells expressing EGFR but did not bind to the EGFR-negative cells. With all of the aforementioned advantages, the DNA aptamers reported here against cancer biomarker EGFR will facilitate the development of novel targeted cancer detection, imaging and therapy.

Objective We assessed the relationship between cerebral ischemia-induced changes in evoked potentials and the degree of ischemia tolerance. Methods 47 patients underwent somatosensory evoked potential (SEP) and motor evoked potential (MEP) monitoring in intracranial aneurysm surgery. Three duration parameters (time) were recorded: Time 1, from the starting of temporary occlusion unavoidable in aneurysm surgery to the time the evoked potentials decrease from basal level to reaching the warning criterion; Time 2, from evoked potentials reaching the warning criterion to the time the blood flow was resumed; Time 3, after resuming the blood flow, the time it took the evoked potentials to recover to baseline. All three times can be reliably calculated in the SEP recording, but not in the MEP recording which consisted of either unchanged amplitudes or abruptly changing amplitudes, making it impossible to obtain Time 1. The ischemic tolerance ratio (ITR) was calculated as ITR = time 2/time 1 × 100%. New decreasing myodynamia and fresh infarction after the surgery were employed for evaluating neurological deficits postoperatively, and their correlations with the ischemia-induced changes of evoked potentials recorded during the surgery were analyzed. Results We found a change in SEPs in 12 patients whose cerebral ischemia was induced by temporary occlusion of the aneurysm's parent artery. We also found the development of postoperative neurological deficits in 4 patients whose ischemic tolerance ratio (ITR) reached over 80%, while no deficits were found in the other 8 patients whose ITR was less than 50%. MEP changes were seen in 4 patients whose cerebral ischemia was caused by accidentally clamping the perforating branches, causing the development of postoperative neurological deficits but not necessarily leading to significant SEP changes. Conclusion The Ischemia tolerance ratio (ITR) in SEP recordings is valuable to predicting postoperative neurological deficits caused by temporary occlusion of aneurysm's parent artery. Maintaining the ITR under 50% during operation can effectively avoid postoperative neurological deficits, while an ITR above 80% reliably forecasts postoperative neurological deficits. Complementary to SEPs, MEP recordings are particularly valuable in monitoring ischemic effects caused by accidentally clamping perforating branches. Taken together, this system of monitoring makes it possible to promptly adjust surgery procedures and minimize postoperative neurological deficits.