Negative symptoms of schizophrenia profoundly affect patients' social function and life quality, and traditional treatments have limited efficacy in improving these symptoms. In recent years, non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS) have shown potentiality in alleviating negative symptoms. However, the selection of stimulation targets remains an area of active research, as different targets may yield varying therapeutic outcomes. Therefore, identifying the most appropriate treatment targets is crucial for improving negative symptoms. This article reviews the targets selection and therapeutic effects of different non-invasive brain stimulation techniques for ameliorating negative symptoms, to provide guidance for target selection in clinical treatment.

During the gene editing process mediated by CRISPR/Cas9, precise genome editing and gene knock-in can be achieved by the homologous recombination of double-stranded DNA (dsDNA) donor template. However, the low-efficiency of homologous recombination in eukaryotic cells hampers the development and application of this gene editing strategy. Here, we developed a novel CRISPR/Cas9-hLacI donor adapting system (DAS) to enhance the dsDNA-templated gene editing, taking the advantage of the specific binding of the LacI repressor protein and the LacO operator sequence derived for the Escherichia coli lactose operon. The codon-humanized LacI gene was fused as an adaptor to the Streptococcus pyogenes Cas9 (SpCas9) and Staphylococcus lugdunensis Cas9 (SlugCas9-HF) genes, and the LacO operator sequence was used as the aptamer and linked to the dsDNA donor template by PCR. The Cas9 nuclease activity after the fusion and the homology-directed repair (HDR) efficiency of the LacO-linked dsDNA template were firstly examined using surrogate reporter assays with the corresponding reporter vectors. The CRISPR/Cas9-hLacI DASs mediated genome precise editing were further checked, and we achieved a high efficiency up to 30.5% of precise editing at the VEGFA locus in HEK293T cells by using the CRISPR/SlugCas9-hLacI DAS. In summary, we developed a novel CRISPR/Cas9-hLacI DAS for dsDNA-templated gene editing, which enriches the CRISPR/Cas9-derived gene editing techniques and provides a novel tool for animal molecular design breeding researches.
Humans ; Animals ; Gene Editing ; CRISPR-Cas Systems/genetics* ; HEK293 Cells ; Homologous Recombination ; DNA

Objective:To explore differences of resting brain regional homogeneity (ReHo) between patients with major depressive disorder (MDD) and their siblings.Methods:From January to December 2013, the resting-state functional magnetic resonance imaging (fMRI) data of 87 patients with MDD and 21 healthy siblings were collected.DPABI v5.1 software was used to preprocess the resting-state fMRI data, and ReHo maps of each subject was obtained. A two-sample t-test was used to compare differences between the patients with MDD and their siblings in ReHo values throughout the brain. ReHo values within the significant brain regions were extracted out, and used to calculate Spearman correlation with the total score of 17-items Hamilton depression rating scale(HAMD-17) in the patients with MDD and their siblings respectively.The software of SPSS 20.0 was used for statistical analysis. Results:The patients with MDD exhibited lower ReHo values in the precuneus extending to the posterior cingulate cortex (PCu/PCC) compared with their siblings (cluster-size=126 voxel, cluster-level PFDR=0.033; MNI: x=-4, y=-58, z=38, t=4.30). ReHo values of the PCu/PCC in patient with MDD were positively correlated with the severity of depressive symptoms ( r=0.255, P=0.021). Conclusion:Compared with the siblings, local brain activity of the PCu/PCC in the patients with MDD was decreased, and related to the severity of depressive symptoms. It is helpful to further reveal the intrinsic neural mechanism of MDD.

The research on clinical high-risk for psychosis is a hotspot in recent years, which is helpful to the early identification and early intervention of psychosis. White matter fibers are the important structural basis of complex information transmission function among brain regions. The existing literatures show that there are abnormal white matter microstructures in individuals at clinical high-risk for psychosis, which is related to their clinical symptoms and social function. Diffusion tensor imaging is the only non-invasive technique to study the microstructure of brain white matter. This paper reviews the existing evidences of microstructural abnormalities of white matter at clinical high-risk for psychosis by diffusion tensor imaging, in order to comprehensively analyze the potential neurobiomarkers in the early stage of the disease and the pathological evolution characteristics in the development of the disease.

Objective:To investigate the correlation between white matter hyperintensities (WMHs) and the outcomes after reperfusion therapy in patients with acute ischemic stroke (AIS).Methods:Patients with AIS treated with reperfusion therapy (intravenous thrombolysis, endovascular mechanical thrombectomy or bridging therapy) in the Stroke Center of Zhongshan Hospital of traditional Chinese Medicine from January 2014 to December 2019 were retrospectively enrolled. The clinical baseline data of the patients were collected. The Fazekas scale was used to evaluate the severity of WMHs according to the MRI images. At 90 d after discharge, the modified Rankin Scale was used to evaluate the outcomes. A score of ≤ 2 was defined as good outcome, and a score of >2 was defined as poor outcome. Binary multivariate logistic regression analysis was used to determine the independent risk factors for hemorrhagic transformation (HT), symptomatic intracranial hemorrhage (sICH), and poor outcomes. Results:A total of 676 patients with AIS treated with reperfusion therapy were enrolled. Among them, 506 patients (74.9%) were complicated with WMHs, and 80 (11.8%) had severe WMHs. One hundred and thirty-two patients (19.5%) had HT, 34 (5.0%) had sICH, and 306 (45.3%) had a poor outcome. Multivariate logistic regression analysis showed that severe WMHs was an independent risk factor for the occurrence of HT (odds ratio [ OR] 1.890, 95% confidence interval [ CI] 1.047-3.413; P=0.035) and poor outcomes ( OR 3.366, 95% CI 1.567-7.232; P=0.002) after reperfusion treatment in patients with AIS, but there was no independent correlation with sICH ( OR 8.403, 95% CI 0.891-79.294; P=0.063). Conclusion:Severe WMHs is an independent risk factor for the occurrence of HT and poor outcomes in patients with AIS after reperfusion treatment, but it has no independent correlation with sICH.

Objective:To investigate the correlations of collateral circulation with hemorrhagic transformation (HT) and short-term prognoses in patients with acute ischemic stroke (AIS) after different reperfusion therapies.Methods:Four hundred and forty-nine patients with AIS after different reperfusion therapies, admitted to our hospital from January 2016 to December 2019, were chosen in our study. These patients were divided into HT group ( n=90) and non-HT group ( n=359) according to whether HT presented or not. The baseline data, clinical characteristics, and prognoses of patients between the 2 groups were compared. And the variables of P<0.05 in univariate analysis were re-analyzed by multivariate Logistics regression to identify the independent influencing factors for HT in patients with AIS; the correlations between cerebral collateral circulation grading (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology [ASITN/SIR], and modified Thrombolysis in Cerebral Infarction [mTICI]) and modified Rankin scale (mRS) scores at discharge were explored. Results:(1) There were significant differences between patients in the two groups in terms of age, percentages of patients with atrial fibrillation, baseline National Institutes of Health Stroke Scale (NIHSS) scores, emergency blood glucose, platelet count, and percentages of patients used dual antiplatelet agents and statin ( P<0.05). (2) Results of multivariate Logistics analysis: moderate stroke (NIHSS scores of 9-15), severe stroke (NIHSS scores≥16), elevated emergency glucose, atherosclerotic cerebral infarction and bridging therapy were independent risk factors for HT, and good collateral circulation status and dual antiplatelet therapy were independent protective factors for HT. (3) Correlation of collateral circulation with short-term prognosis: mRS scores of patients at discharge were negatively correlated with ASITN/SIR grading of collateral circulation and mTICI grading ( rs=-0.201, P=0.003; rs=-0.222, P=0.001). Further grouping by different reperfusion therapies showed that ASITN/SIR grading in the intravenous thrombolysis group and mTICI grading in the bridging therapy group were negatively correlated with mRS scores of these patients at discharge ( rs=-0.176, P=0.016; rs=-0.271, P=0.010). Conclusion:AIS patients with poor collateral circulation who receive reperfusion therapies are more likely to develop HT than patients with good collateral circulation, enjoying a relatively poor short-term prognosis.

Reperfusion therapy has become a standard treatment for acute ischemic stroke, which can effectively improve the outcomes of patients and reduce the mortality. Some studies have found that reperfusion therapy may increase the incidence of post-stroke seizures and post-stroke epilepsy, but this view is still controversial. This article reviews the recent studies on reperfusion therapy and post-stroke seizures and post-stroke epilepsy.

Objective To explore the influence of gender and age on auditory startle reflex in healthy adults.Methods A total of 150 healthy volunteers (92 males and 58 females) aged from 18 to 60 years were recruited for this study.A modified startle reflex paradigm was adopted.Furthermore,gender-age differences on startle magnitude,habituation,perceived spatial co-location induced prepulse inhibition (PSC-PPI) and perceived spatial separation-induced prepulse inhibition (PSS-PPI) in healthy volunteers were analyzed.Results ① There was no significant difference in amplitude and habituation of startie reflex between males and females (F=0.29,P=0.593;F=1.57,P=0.212).PSC-PPI and PSS-PPI were significantly higher in males (PSC-PPI:(34.68± 20.81) ％,PSS-PPI:(44.56 ± 23.19) ％) than those in females (PSC-PPI:(23.11±22.43)％,PSS-PPI:(35.21±25.09)％) (F=9.48,P=0.002;F=4.76,P=0.031).② There was a negative correlation between startle magnitude and age (r=-0.29,P＜0.01),however,no obvious correlations between age and PSC-PPI or PSS-PPI as well as habituation were observed.③Bivariate analysis of variance showed that no interaction between gender and age was found to the indexes of startle reflex(F=0.71-1.36,all P＞0.05).Conclusions There are differences for gender and age in the indexes of startle reflex.In detail,age chiefly influences startle magnitude,while gender mainly affects the prepulse inhibition.

Objective To evaluate the accuracy of a novel echocardiographic three-dimensional automated software for the assessment of the aortic root in candidates for transcatheter aortic valve replacement(TAVR).Methods Four patterns(Lax,Lax-Res,Sax,Sax-Res) of 3D-TEE imaging of aortic root were gotten preoperatively in 18 patients with severe tricuspid aortic stenosis who were referred to our center for TAVR.The specialized 3D-TEE reconstruction software,eSie Valves,then automatically configured a geometric model of the aortic root from the images obtained by 3D-TEE and performed a quantitative analysis of these structures:the minimal diameter(Dmin),maximal diameter(Dmax),area and perimeter(Peri) of aortic annulus,height of the ostia of the left/right coronary artery above the aortic annulus(LOH/ROH).The echo dimensions were compared with the MDCT measurements.Results No statistically significant difference were found in above parameters between the ZOOM pattern (Sax-Res and Lax-Res) and CT measurements(all P>0.05).Lax-Res pattern measurements had good correlation with MDCT,with r valves of 0.81,0.77,0.89,0.84 for Lax-Res-Dmin,Lax-Res-Dmax,Lax-Res-Area,Lax-Res-Peri,respectively(all P<0.05).3D-TEE LOH/ROH had poor correlation with MDCT LOH/ROH (all r<0.7).Conclusions The new automatic 3D-TEE software allows modelling and quantifying the aortic annulus dimensions from 3D-TEE data in patients with tricuspid aortic valves,and Lax-Res pattern is recommended.Quantified assessment of LOH/ROH is not ideal and needs to be improved.

Aortic Valve Insufficiency ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Transcatheter Aortic Valve Replacement