Larger deep white matter hyperintensity volume correlates with more severe social behavioral changes in patients with subacute ischemic stroke.

Background: Changes in social behavior can occur after ischemic stroke. We aimed to investigate the potential correlations between neuroimaging variables and changes in social behavior in patients who experienced subacute ischemic stroke. Methods: We prospectively screened patients with first-ever ischemic stroke. Three months after the index stroke, changes in patients' social behavior were investigated by the Frontal Behavioral Inventory (FBI), which consists of both deficit and positive groups of behaviors. The protocol of brain magnetic resonance imaging (MRI) including the baseline MRI at the acute stage and additional MRI with three-dimensional T1-weighted imaging on follow-up. Using these MRI scans, we assessed the acute infarction and the volumes of various brain structures by an automatic volumetry tool. Results: Eighty patients were enrolled. In univariate analyses, patients with deficit behavioral changes had more left cortical infarction (r = 0.271, p = 0.015), Cholinergic Pathways Hyperintensities Scale scores (r = 0.227, p = 0.042), DWMH volumes (r = 0.349, p = 0.001), and modified Rankin Scale (mRS) scores (r = 0.392, p < 0.001). Patients with positive behavioral changes had more frequency of men (r = 0.229, p = 0.041) and a history of hypertension (r = 0.245, p = 0.028). In multiple stepwise linear regression models, after adjusting for age, deep WMH volumes (ß = 0.849, 95% confidence interval = 0.352-1.346, p = 0.001) and mRS scores on follow-up (ß = 1.821, 95% confidence interval = 0.881-2.76, p < 0.001) were significantly correlated with deficit behavioral changes (R2 = 0.245). Conclusion: Larger deep WMH volumes and poorer mRS scores on follow-up were significantly correlated with deficit behavioral changes in patients with subacute ischemic stroke.

Right Cortical Infarction and a Reduction in Putamen Volume May Be Correlated with Empathy in Patients after Subacute Ischemic Stroke-A Multimodal Magnetic Resonance Imaging Study.

Empathy has not been well studied in patients following ischemic stroke. We aimed to evaluate the relationships of multimodal neuroimaging parameters with the impairment of empathy in patients who had experienced subacute ischemic stroke. Patients who had experienced a first-event acute ischemic stroke were recruited, and we assessed their empathy using the Chinese version of the Empathy Quotient (EQ) 3 months after the index stroke. Multimodal magnetic resonance imaging (MRI) was conducted in all the participants to identify acute infarction and assess brain volumes, white matter integrity, and other preexisting abnormalities. We quantified the brain volumes of various subcortical structures, the ventricles, and cortical lobar atrophy. The microstructural integrity of the white matter was reflected in the mean fractional anisotropy (FA) and mean diffusivity (MD), and the regional mean values of FA and MD were quantified after mapping using the ICBM_DTI_81 Atlas. Twenty-three (56.1%) men and 18 (43.9%) women (mean age: 61.73 years, range: 41-77 years) were included. The median National Institutes of Health Stroke Scale (NIHSS) score at discharge was 1 (range: 0-4). On univariate analysis, the EQ was correlated with right cortical infarction (r = -0.39, p = 0.012), putamen volume (r = 0.382, p = 0.014), right putamen volume (r = 0.338, p = 0.031), and the FA value of the right sagittal stratum. EQ did not correlated with the MD value in any region of interest or pre-existing brain abnormalities. Multiple stepwise linear regression models were used to identify factors associated with EQ. After adjusting for age and the NIHSS score on admission, the frequency of right cortical infarcts negatively correlated with EQ (standardized ß = -0.358, 95% confidence interval =-0.708 to -0.076, p = 0.016), and the putamen volume positively correlated with EQ (standardized ß = 0.328, 95% confidence interval =0.044 to 0.676, p = 0.027). In conclusion, in patients who have experienced subacute ischemic stroke, right cortical infarction and a smaller putamen volume are associated with the impairment of empathy.

Advances on research of physical environment affecting stem cell differentiation in ligament tissue engineering / 中国骨伤

Ligament tissue engineering is currently a novel approach to the treatment of ligament injury, which can replace the deficiency of autografts. Ligament tissue engineering consists of four basic elements:seed cells, nanoscaffolds, growth factors, and mechanical stimulation. At present, the main problem in ligament tissue engineering is how to control seed cells to ligament cells more controllly. The study found that each physical property of the natural bio ligament and mechanical stimulation (uniaxial stretching) plays an important role in the differentiation of stem cells into ligament cells. Therefore, the design of nanofiber scaffolds must consider the elastic modulus of the material and the material. Structure(material arrangement, porosity and diameter, etc.), elastic modulus and material structure in different ranges will guide cells to differentiate into different lineages. Considering that the ligament is the main force-bearing tissue of the human body, mechanical stimulation is also essential for stem cell differentiation, especially uniaxial stretching, which best meets the stress of the ligament in the body. A large number of studies have found the frequency and amplitude of stretching. And time will also lead the cells to differentiate in different directions. RhoA/ROCK plays a regulatory role in cytoskeletal remodeling and cell differentiation. It is also found that RhoA/ROCK protein participates in the process of nanofiber arrangement and uniaxial stretching to guide stem cells to differentiate into ligament cells, specifically how to influence stem cell differentiation. It is not clear at present that understanding the effects of physical properties on stem cell differentiation and understanding the mechanism of action of RhoA/ROCK protein will provide a new theoretical basis for further optimization of ligament tissue engineering.

CRISPR/Cas9 genome editing system and its application in tumor therapy / 国际肿瘤学杂志

CRISPR/ Cas9 gene editing system is a new tool of gene editing technology based on the im-mune mechanism of archaea against foreign nucleic acid invasion. Due to its high efficiency and accuracy, CRISPR/ Cas9 genome editing technology has been widely used in tumor therapeutic research,such as targeted knockout of oncogenes,repair of tumor suppressor genes,breaking immune tolerance,and construction of tumor models,which brings revolutionary development to tumor gene therapy.

Generalization of the Right Acute Stroke Prevention Strategies in Reducing in-Hospital Delays.

The aim of this study was to reduce the door-to-needle (DTN) time of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) through a comprehensive, hospital-based implementation strategy. The intervention involved a systemic literature review, identifying barriers to rapid IVT treatment at our hospital, setting target DTN time intervals, and building an evolving model for IVT candidate selection. The rate of non-in-hospital delay (DTN time ≤ 60 min) was set as the primary endpoint. A total of 348 IVT cases were enrolled in the study (202 and 146 in the pre- and post-intervention group, respectively). The median age was 61 years in both groups; 25.2% and 26.7% of patients in the pre- and post-intervention groups, respectively, were female. The post-intervention group had higher rates of dyslipidemia and minor stroke [defined as National Institutes of Health Stroke Scale (NIHSS) ≤ 3]; less frequent atrial fibrillation; higher numbers of current smokers, heavy drinkers, referrals, and multi-model head imaging cases; and lower NIHSS scores and blood sugar level (all P < 0.05). All parameters including DTN, door-to-examination, door-to-imaging, door-to-laboratory, and final-test-to-needle times were improved post-intervention (all P < 0.05), with net reductions of 63, 2, 4, 28, and 23 min, respectively. The rates of DTN time ≤ 60 min and onset-to-needle time ≤ 180 min were significantly improved by the intervention (pre: 9.9% vs. post: 60.3%; P < 0.001 and pre: 23.3% vs. post: 53.4%; P < 0.001, respectively), which was accompanied by an increase in the rate of neurological improvement (pre: 45.5% vs. post: 59.6%; P = 0.010), while there was no change in incidence of mortality or systemic intracranial hemorrhage at discharge (both P > 0.05). These findings indicate that it is possible to achieve a DTN time ≤ 60 min for up to 60% of hospitals in the current Chinese system, and that this logistical change can yield a notable improvement in the outcome of IVT patients.

Factors Associated with In-Hospital Delay in Intravenous Thrombolysis for Acute Ischemic Stroke: Lessons from China.

In-hospital delay reduces the benefit of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS), while factors affecting in-hospital delay are less well known in Chinese. We are aiming at determining the specific factors associated with in-hospital delay through a hospital based cohort. In-hospital delay was defined as door-to-needle time (DTN) ≥60 min (standard delay criteria) or ≥75% percentile of all DTNs (severe delay criteria). Demographic data, time intervals [onset-to-door time (OTD), DTN, door-to-examination time (DTE), door-to-imaging time (DTI), door-to-laboratory time (DTL) and final-test-to-needle time (FTN, the time interval between the time obtaining the result of the last screening test and the needle time)], medical history and additional variables were calculated using Mann-Whitney U or Pearson Chi-Square tests for group comparison, and multivariate linear regression analysis was performed to identify independent variables of in-hospital delay. A total of 202 IVT cases were enrolled. The median age was 61 years and 25.2% were female. The cutoff points for the upper quartile of DTN (severe delay criteria) was 135 min.When compared with the reference group without in-hospital delay, older age, shorter OTD and less referral were found in the standard delay group and male sex, presence with transient ischemic attacks or rapidly improving symptom, and with multi-model CT imaging were more frequent in the severe delay group. In the multivariate linear regression analysis, FTN (P<0.001) and DTL (P = 0.002) were significantly associated with standard delay; while DTE (P = 0.005), DTI (P = 0.033), DTL (P<0.001), and FTN (P<0.001) were positively associated with severe delay. There was not a significant change in the trend of DTNs during the study period (P = 0.054). In-hospital delay was due to multifactors in China, in which time delays of decision-making process and laboratory tests contributed the most. Efforts aiming at reducing the delay should be focused on the optimization for the items of screening tests and improvement of the pathway organization.