In computer-assisted diagnostics, assessing the quality of retinal images, especially for DR, is vital. While current Image Quality Assessment (IQA) methods lean on Transfer Learning (TL), their adaptability to specific IQA demands, especially for DR images, remains questionable due to the challenges of detecting detailed distortions. In this paper, we propose a novel framework termed Saliency-Aware Mutual Learning for Image Quality Assessment (SAM-IQA). This framework intricately learns the relationship between the representation of salient regions and the overall representation of fundus images. Specifically, we introduce a dual-branch network architecture that simultaneously extracts global features from distorted images and local features from their salient regions. This dual extraction promotes the learning of both coarse and fine-grained feature representations. To further enhance feature extraction, we integrate mutual learning techniques within this dual-branch network, facilitating the capture of high-level content presentation and low-level fusion quality features. This integration results in a more holistic quality assessment. Our evaluation of the DeepDRiD dataset demonstrates the efficacy of SAM-IQA. The method achieved an AUC of 81.5% (↑6.6% vs. previous state-of-the-art (SOTA) methods of 74.9%), outperforming existing IQA methods.

BACKGROUND:Type 2 diabetes has been shown to reduce the risk of migraine, whereas insulin resistance (IR) is often elevated in migraineurs. The triglyceride glucose index (TyG) serves as a reliable surrogate marker of IR, which has been hypothesized to be associated with migraine pathophysiology. This study aimed to examine the relationship between TyG index scores and incidence as well as the severity of migraines through both cohort and cross-sectional analyses. METHODS:Using data from the China Health and Retirement Longitudinal Study (CHARLS), we evaluated migraine incidence between 2015 and 2020. TyG index values were calculated using the following formula: ln[fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The impact of TyG index scores on the incidence of migraines was assessed using a multivariate-adjusted Cox regression model. The cross-sectional study included 161 patients with migraines in Xiamen, China. The relationship between TyG index scores and different migraine characteristics was examined using multivariable and ordered logistic regression models with further subgroup analysis by migraine course. RESULTS:Among the cohort participants, 1001 new migraine cases were identified during follow-up, with no significant relationship found between TyG index scores and migraine incidence (hazard ratio = 1.024 (0.916, 1.145), p = 0.677 > 0.05). The cross-sectional study showed that migraine-related disability was significantly lower among patients in the second, third and fourth quartiles of TyG index scores compared to the first quartile (odds ratio = 0.402 (0.163, 0.973), 0.322 (0.128, 0.789) and 0.301 (0.119, 0.736), respectively; ptrend = 0.009). A similar trend was observed in patients with migraine history of less than ten years. CONCLUSIONS:Integrating the results of both cohort and cross-sectional studies, this study suggests that IR may play a protective role in the early stages of migraine. Further research into the relevant underlying mechanisms could aid in identifying new therapeutic targets for migraine management.

BackgroundMigraine is a common primary headache that has a significant impact on patients’ quality of life. The co-occurrence of migraine and depression is frequent, resulting in more complex symptoms and a poorer prognosis. The evidence suggests that depression and migraine comorbidity share a polygenic genetic background.ObjectiveThe aim of this study is to identify related genetic variants that contribute to genetic susceptibility to migraine with and without depression in a Chinese cohort.MethodsIn this case-control study, 263 individuals with migraines and 223 race-matched controls were included. Eight genetic polymorphism loci selected from the GWAS were genotyped using Sequenom’s MALDI-TOF iPLEX platform.ResultsIn univariate analysis, ANKDD1B rs904743 showed significant differences in genotype and allele distribution between migraineurs and controls. Furthermore, a machine learning approach was used to perform multivariate analysis. The results of the Random Forest algorithm indicated that ANKDD1B rs904743 was a significant risk factor for migraine susceptibility in China. Additionally, subgroup analysis by the Boruta algorithm showed a significant association between this SNP and migraine comorbid depression. Migraineurs with depression have been observed to have worse scores on the Beck Anxiety Inventory (BAI) and the Migraine Disability Assessment Scale (MIDAS).ConclusionThe study indicates that there is an association between ANKDD1B rs904743 and susceptibility to migraine with and without depression in Chinese patients.

Aim: We aimed to explore the relationship between type 2 diabetes mellitus (T2DM) and the incidence rate of migraine in a Chinese population, and analyze the clinical characteristics of migraine patients with T2DM. Methods: Data on the study cohort of 9873 individuals were obtained from the China Health and Retirement Longitudinal Study (CHARLS). The incidence rate of migraine from 2015 to 2018 was assessed. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs) for the relationship between T2DM and the incidence of migraine. In addition, a cross-sectional study including 168 migraine patients was conducted in Xiamen, China. Migraine patients were grouped according to their T2DM status. Multivariable linear regression models were used to estimate beta s and their 95% CIs for the relationship between migraine characteristics and T2DM. Results: The cumulative incidence rate of migraine from 2015 to 2018 in the T2DM group and control group was 7.26% [6.04%.8.65%] and 8.91% [8.27%.9.58%], respectively. The risk of migraine in patients with T2DM was reduced by 21% (HR 0.79 [0.65;0.95]) compared to patients with no T2DM after adjustment for confounders. The cross-sectional study showed that the presence of T2DM significantly reduced migraine frequency and relieved migraine intensity. Conclusion: This was the first study to validate that T2DM reduced the risk of migraine in a Chinese population cohort. Patients with migraine and T2DM may experience significant relief from their headache symptoms. Carrying out relevant mechanistic research may help to identify new targets for migraine treatment and contribute to further understanding the impact of T2DM or related metabolic disorders on an individual's health.

Introduction The incidence of cancer-associated ischaemic stroke (IS) is increasingly prevalent. This study aimed to assess the levels of enlarged perivascular spaces in basal ganglion (BG-EPVS) in cancer-associated patients who had a stroke compared with the control group, and to investigate the diagnostic utility of BG-EPVS in the context of cancer-associated stroke.Method A matched case–control study was conducted in Xiamen, China. A total of 184 IS patients (cancer vs control=1:1) were recruited. The severity of BG-EPVS was graded using high-resolution MRI. Patients’ gender, age, clinical risk factors, other imaging changes and laboratory findings information at admission were collected. Logistic regression models were constructed and subgroup analysis by cancer treatment.Result Overall, 65.22% of the 184 subjects were male, with a mean (SD) age of 68.83±10.52 years. BG-EPVS had a significant influence on cancer-associated stroke (OR=1.85 (95% CI 1.29, 2.71), p=0.001) after adjusting for gender, age, clinical risk factors, other imaging changes and laboratory findings. The area under the curve of the diagnosis model that combined BG-EPVS and other factors was 0.848 (95% CI 0.787, 0.896), significantly higher than the other three models. Subgroup analysis suggested a heightened association between BG-EPVS and cancer-associated stroke within the cancer treatment group.Conclusion In conclusion, this is the first study to assess the diagnosis values of BG-EPVS on cancer-associated stroke and helps us understand the pathogenesis of cancer-associated stroke. Our findings demonstrate the effectiveness of BG-EPVS in diagnosing IS patients who may carry underlying cancer.

Background/aims The reciprocal promotion of cancer and stroke occurs due to changes in shared risk factors, such as metabolic pathways and molecular targets, creating a “vicious cycle.” Cancer plays a direct or indirect role in the pathogenesis of ischemic stroke (IS), along with the reactive medical approach used in the treatment and clinical management of IS patients, resulting in clinical challenges associated with occult cancer in these patients. The lack of reliable and simple tools hinders the effectiveness of the predictive, preventive, and personalized medicine (PPPM/3PM) approach. Therefore, we conducted a multicenter study that focused on multiparametric analysis to facilitate early diagnosis of occult cancer and personalized treatment for stroke associated with cancer. Methods Admission routine clinical examination indicators of IS patients were retrospectively collated from the electronic medical records. The training dataset comprised 136 IS patients with concurrent cancer, matched at a 1:1 ratio with a control group. The risk of occult cancer in IS patients was assessed through logistic regression and five alternative machine-learning models. Subsequently, select the model with the highest predictive efficacy to create a nomogram, which is a quantitative tool for predicting diagnosis in clinical practice. Internal validation employed a ten-fold cross-validation, while external validation involved 239 IS patients from six centers. Validation encompassed receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and comparison with models from prior research. Results The ultimate prediction model was based on logistic regression and incorporated the following variables: regions of ischemic lesions, multiple vascular territories, hypertension, D-dimer, fibrinogen (FIB), and hemoglobin (Hb). The area under the ROC curve (AUC) for the nomogram was 0.871 in the training dataset and 0.834 in the external test dataset. Both calibration curves and DCA underscored the nomogram’s strong performance. Conclusions The nomogram enables early occult cancer diagnosis in hospitalized IS patients and helps to accurately identify the cause of IS, while the promotion of IS stratification makes personalized treatment feasible. The online nomogram based on routine clinical examination indicators of IS patients offered a cost-effective platform for secondary care in the framework of PPPM.

目的 调查临床护理人员血液标本采集知识的现状,为提高血液标本采集质量提供依据.方法 采用便利抽样方法,于 2022 年 4-5 月选取厦门市某三级甲等综合性医院的在职临床护理人员作为调查对象,采用一般资料调查表和临床血液标本采集知识现状凋查表对其进行调查.结果 313 名护理人员临床血液标本采集知识总得分为 8～24 分,平均(18.31±2.58)分,总得分率为 73.24％.其中护理人员对血常规标本送检的时间、采血后真空采血管颠倒的时间、快步行走后的休息时间、松开止血带的时间、采血前静息时间的知晓率较低,分别为 21.73％、28.75％、30.35％、44.41％、46.65％.68.69％的临床护理人员通过科室学习了解到临床血液标本采集内容,92.01％的护理人员希望能举办业务学习从而获得更多类似的采血临床指南知识.结论 临床护理人员对血液标本采集知识掌握程度处于中等水平,应进一步加强对护理人员相关知识的培训和考核,规范操作流程,提高血样采集质量.

Background: Thrombolysis is the first-line treatment for patients with acute ischemic stroke. Previous studies leveraged machine learning to assist neurologists in selecting patients who could benefit the most from thrombolysis. However, when designing the algorithm, most of the previous algorithms traded interpretability for predictive power, making the algorithms hard to be trusted by neurologists and be used in real clinical practice. Methods: Our proposed algorithm is an advanced version of classical k-nearest neighbors classification algorithm (KNN). We achieved high interpretability by changing the isotropy in feature space of classical KNN. We leveraged a cohort of 189 patients to prove that our algorithm maintains the interpretability of previous models while in the meantime improving the predictive power when compared with the existing algorithms. The predictive powers of models were assessed by area under the receiver operating characteristic curve (AUC). Results: In terms of interpretability, only onset time, diabetes, and baseline National Institutes of Health Stroke Scale (NIHSS) were statistically significant and their contributions to the final prediction were forced to be proportional to their feature importance values by the rescaling formula we defined. In terms of predictive power, our advanced KNN (AUC 0.88) out-performed the classical KNN (AUC 0.75, p= 0.0192). Conclusions: Our preliminary results show that the advanced KNN achieved high AUC and identified consistent significant clinical features as previous clinical trials/observational studies did. This model shows the potential to assist in thrombolysis patient selection for improving the successful rate of thrombolysis.

Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease (AD). High-frequency stimulation (HFS)-induced long-term potentiation (LTP) has been widely used to study synaptic plasticity, with impaired LTP found to be associated with AD. However, the exact molecular mechanism underlying synaptic plasticity has yet to be completely elucidated. Whether genes regulating synaptic plasticity are altered in AD and contribute to disease onset also remains unclear. Herein, we induced LTP in the hippocampal CA1 region of wild-type (WT) and AD model mice by administering HFS to the CA3 region and then studied transcriptome changes in the CA1 region. We identified 89 genes that may participate in normal synaptic plasticity by screening HFS-induced differentially expressed genes (DEGs) in mice with normal LTP, and 43 genes that may contribute to synaptic dysfunction in AD by comparing HFS-induced DEGs in mice with normal LTP and AD mice with impaired LTP. We further refined the 43 genes down to 14 by screening for genes with altered expression in pathological-stage AD mice without HFS induction. Among them, we found that the expression of Pygm, which catabolizes glycogen, was also decreased in AD patients. We further demonstrated that down-regulation of PYGM in neurons impaired synaptic plasticity and cognition in WT mice, while its overexpression attenuated synaptic dysfunction and cognitive deficits in AD mice. Moreover, we showed that PYGM directly regulated energy generation in neurons. Our study not only indicates that PYGM-mediated energy production in neurons plays an important role in synaptic function, but also provides a novel LTP-based strategy to systematically identify genes regulating synaptic plasticity under physiological and pathological conditions.

Purpose Serum neurofilament light chain (sNfL) can reflect nerve damage. Whether migraine can cause neurological damage remain unclear. This study assesses sNfL levels in migraine patients and explores whether there is nerve damage in migraine. Methods A case–control study was conducted in Xiamen, China. A total of 138 migraine patients and 70 healthy controls were recruited. sNfL (pg/mL) was measured on the single-molecule array platform. Univariate, Pearson correlation and linear regression analysis were used to assess the relationship between migraine and sNfL levels, with further subgroup analysis by migraine characteristics. Results Overall, 85.10% of the 208 subjects were female, with a median age of 36 years. sNfL levels were higher in the migraine group than in the control group (4.85 (3.49, 6.62) vs. 4.11 (3.22, 5.59)), but the difference was not significant ( P = 0.133). The two groups showed an almost consistent trend in which sNfL levels increased significantly with age. Subgroup analysis showed a significant increase in sNfL levels in patients with a migraine course ≥ 10 years (β = 0.693 (0.168, 1.220), P = 0.010). Regression analysis results show that age and migraine course are independent risk factors for elevated sNfL levels, and there is an interaction between the two factors. Patients aged < 45 years and with a migraine course ≥ 10 years have significantly increased sNfL levels. Conclusions This is the first study to evaluate sNfL levels in migraine patients. The sNfL levels significantly increased in patients with a migraine course ≥ 10 years. More attention to nerve damage in young patients with a long course of migraine is required.

In the treatment of ischemic stroke, timely and efficient recanalization of occluded brain arteries can successfully salvage the ischemic brain. Thrombolysis is the first-line treatment for ischemic stroke. Machine learning models have the potential to select patients who could benefit the most from thrombolysis. In this study, we identified 29 related previous machine learning models, reviewed the models on the accuracy and feasibility, and proposed corresponding improvements. Regarding accuracy, lack of long-term outcome, treatment option consideration, and advanced radiological features were found in many previous studies in terms of model conceptualization. Regarding interpretability, most of the previous models chose restrictive models for high interpretability and did not mention processing time consideration. In the future, model conceptualization could be improved based on comprehensive neurological domain knowledge and feasibility needs to be achieved by elaborate computer science algorithms to increase the interpretability of flexible algorithms and shorten the processing time of the pipeline interpreting medical images.

目的 比较巴曲酶不同应用时机对急性脑梗死(ACI)患者神经功能的影响.方法 选择2019年9月至2020年8月我院收治的136例ACI患者,随机分为两组各68例.对照组入院12 h后给予巴曲酶,观察组入院后即刻给予巴曲酶,之后隔日用药1次,连续治疗14 d.对比两组的临床疗效、神经功能缺损状况、凝血功能、不良反应.结果 观察组治疗总有效率高于对照组(P<0.05).治疗前,两组的NIHSS评分、FIB水平比较无统计学差异(P>0.05);治疗后,观察组的NIHSS评分、FIB水平低于对照组(P<0.05).两组患者治疗前后的PT比较无统计学差异(P<0.05).两组的不良反应发生率比较无统计学差异(P>0.05).结论 ACI患者入院后即刻采用巴曲酶治疗效果更佳,可明显减轻神经功能缺损状况,改善凝血功能,利于症状快速缓解,应用价值较高.

Apolipoprotein E (APOE) plays a pivotal role in lipid including cholesterol metabolism. The APOE ε4 (APOE4) allele is a major genetic risk factor for Alzheimer's and cardiovascular diseases. Although APOE has recently been associated with increased susceptibility to infections of several viruses, whether and how APOE and its isoforms affect SARS-CoV-2 infection remains unclear. Here, we show that serum concentrations of APOE correlate inversely with levels of cytokine/chemokine in 73 COVID-19 patients. Utilizing multiple protein interaction assays, we demonstrate that APOE3 and APOE4 interact with the SARS-CoV-2 receptor ACE2; and APOE/ACE2 interactions require zinc metallopeptidase domain of ACE2, a key docking site for SARS-CoV-2 Spike protein. In addition, immuno-imaging assays using confocal, super-resolution, and transmission electron microscopies reveal that both APOE3 and APOE4 reduce ACE2/Spike-mediated viral entry into cells. Interestingly, while having a comparable binding affinity to ACE2, APOE4 inhibits viral entry to a lesser extent compared to APOE3, which is likely due to APOE4's more compact structure and smaller spatial obstacle to compete against Spike binding to ACE2. Furthermore, APOE ε4 carriers clinically correlate with increased SARS-CoV-2 infection and elevated serum inflammatory factors in 142 COVID-19 patients assessed. Our study suggests a regulatory mechanism underlying SARS-CoV-2 infection through APOE interactions with ACE2, which may explain in part increased COVID-19 infection and disease severity in APOE ε4 carriers.

Recombinant human prourokinase (rhPro-UK) is a novel thrombolytic that has been approved to treat patients with acute myocardial infarction. However, the safety and efficacy of intravenous rhPro-UK in patients with acute ischemic stroke (AIS) has not been well established. We aimed to investigate the safety and preliminary efficacy of rhPro-UK in patients with AIS in a multi-center phase IIa trial setting. One hundred nineteen patients within 4.5 h of AIS onset were enrolled in this randomized, open-label, 23-center phase IIa clinical trial. Patients were randomly assigned to 35 mg (n = 40) or 50 mg (n = 39) intravenous rhPro-UK or 0.9 mg/kg recombinant tissue plasminogen activator (r-tPA; n = 40). The primary endpoint was functional independence defined as a modified Rankin scale (mRS) score of 0 or 1 at 90 days. The secondary outcome was early neurological improvement defined as a reduction of ≥ 4 points on the National Institutes of Health Stroke Scale (NIHSS) score from baseline to 24 h after drug administration. Safety endpoints included death due to any cause, symptomatic intracerebral hemorrhage (sICH), and other serious adverse events (SAEs). The proportion of patients with an mRS score of ≤ 1 at 90 days did not differ significantly among three groups (35 mg rhPro-UK: 55.56 http://www.chictr.org.cn . Identifier: ChiCTR1800016519. Date of registration: June 6 2018.

目的 探讨急性缺血性卒中患者出现MRI液体衰减反转恢复序列血管高信号征(FVH)的影响因素以及FVH与责任血管狭窄因素的关系.方法 回顾性连续纳入2016年1月至2020年1月厦门大学附属第一医院神经内科急性缺血性卒中住院患者360例,于发病72 h内完善头部MR检查,且梗死责任动脉为单侧大脑中动脉(MCA),排除了静脉溶栓或血管内治疗者.给予控制血压、调整血糖等一般治疗及抗血栓治疗.根据患者MRI是否显示FVH,将360例患者分为FVH阴性组[256例(71.1％)]和FVH阳性组[104例(28.9％)].收集并比较FVH阴性组和FVH阳性组患者的人口学资料、临床资料,包括年龄、性别、卒中危险因素[吸烟、饮酒,既往卒中和(或)短暂性脑缺血发作(TIA)、缺血性心脏病、心房颤动、高血压病、糖尿病、高脂血症]、入院时美国国立卫生研究院卒中量表(NIHSS)评分、影像学资料.以FVH阳性为因变量,将单因素分析中P<0.05的自变量纳入FVH阳性影响因素的多因素Logistic回归分析.比较FVH阴性组和FVH阳性组患者MCA狭窄部位及M1段狭窄程度的差异.结果 (1)与FVH阴性组比较,FVH阳性组患者高脂血症比例较低,而心房颤动、既往卒中和(或)TIA比例较高,且入院时NIHSS评分较高,组间差异均有统计学意义[34.6％(36/104)比56.2％(144/256),χ2=13.846;20.2％(21/104)比8.6％(22/256),χ2=9.459;21.2％(22/104)比11.7％(30/256),χ2=5.327;7.5(5.0,12.0)分比5.0(3.0,8.0)分,Z=-5.687;均P<0.05].两组年龄、性别、高血压病、糖尿病、缺血性心脏病、烟酒史的差异均无统计学意义(均P>0.05).(2)FVH阳性影响因素的多因素Logistic回归分析结果显示,高脂血症为FVH阳性的保护因素(OR=0.448,95％CI:0.271～0.742,P=0.002),入院时高NIHSS评分为FVH阳性的危险因素(OR=1.143,95％CI:1.084～1.205,P<0.01);心房颤动、既往卒中和(或)TIA史与FVH阳性无关(均P>0.05).(3)104例FVH阳性组患者中,M1段、M2段、M3段及其远端狭窄比例分别为61.5％(64例)、20.2％(21例)、18.3％(19例),以M1段狭窄比例最高;256例FVH阴性组中,M1段、M2段、M3段及其远端狭窄比例分别为30.9％(79例)、32.0％(82例)、37.1％(95例),以M1段狭窄比例最低,狭窄部位分布的组间差异有统计学意义(χ2=29.436,P<0.01).(4)79例M1段狭窄的FVH阴性组患者中,M1段狭窄轻度、中度、重度或闭塞比例分别为13.9％(11例)、67.1％(53例)、19.0％(15例);64例M1段狭窄的FVH阳性组患者中,M1段狭窄轻度、中度、重度或闭塞比例分别为9.4％(6例)、17.2％(11例)、73.4％(47例),以重度狭窄或完全闭塞比例最高,且高于FVH阴性组,MCA M1段狭窄程度的组间差异有统计学意义(Z=-5.075,P<0.01).结论 入院时高NIHSS评分是FVH出现的危险因素,而高脂血症对FVH出现的影响有待进一步探索.FVH阳性中M1段狭窄比例更高,其中以MCA M1段重度狭窄或闭塞更常见.

Studies have shown that addictive behavior is associated with many brain regions, such as the insula, globus pallidus, amygdala, nucleus accumbens, and midbrain dopamine system, but only a few studies have explored the role of the dorsal striatum in addictive behavior. In June 2020, we started contacting 608 patients who were hospitalized between January 2017 and December 2019, and we recruited 11 smoking addicts with dorsal striatum damage and 20 controls with brain damage that did not involve the dorsal striatum (the damaged areas included the frontal lobe, temporal lobe, parietal lobe, brain stem, thalamus, internal capsule, and so on). All study participants had brain damage due to acute cerebral infarction. Disruption of smoking addiction was found to be significantly associated with the dorsal striatum (Phi = 0.794770, P = 0.000015). Our findings suggested that patients in the dorsal striatum group were more likely to discontinue smoking than those in the non-dorsal striatum group. The characteristics of this interruption is that smoking can be quit more easily and quickly without recurrence and that the impulse to smoke is reduced. These results suggest that the dorsal striatum is a key area for addiction to smoking.

目的:探讨阿替普酶联合阿加曲班在急性脑梗死(ACI)患者中的应用价值.方法:选择2019年3月至2020年10月厦门大学附属第一医院就诊的92例ACI患者,依据随机数字表法分成两组,各46例.对照组予以阿替普酶,观察组加用阿加曲班,连续用药14 d.对比两组临床疗效、神经功能损伤因子、血流动力学指标、不良反应.结果:观察组治疗总有效率为93.48％,高于对照组的78.26％,差异有统计学意义(P<0.05);治疗前,两组神经元特异性烯醇化酶(NSE)、S100β蛋白水平和全血低切黏度(LSV)、全血高切黏度(HSV)比较,差异无统计学意义(P>0.05);治疗后,观察组NSE、S100β蛋白和LSV、HSV水平低于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05).结论:阿替普酶联合阿加曲班能够降低ACI患者神经功能损伤因子水平,改善其血流动力学,效果显著.

White matter lesions known as leukoaraiosis (LA) are cerebral white matter hyperintensities observed in elderly individuals. Currently, no reliable molecular biomarkers are available for monitoring their progression over time. To identify biomarkers for the onset and progression of LA, we analyzed whole blood-based, microRNA expression profiles of leukoaraiosis, validated those exhibiting significant microRNA changes in clinical subjects by means of quantitative real-time polymerase chain reactions and determined the function of miRNA in cell lines by means of microRNA mimic transfection assays. A total of seven microRNAs were found to be significantly down-regulated in leukoaraiosis. Among the microRNAs, hsa-miR-1972 was downregulated during the early onset phase of leukoaraiosis, as confirmed in independent patients, and it was found to target leukoaraiosis-dependent BAIAP3, decreasing its expression in 293T cell lines. Functional enrichment analysis revealed that significantly dysregulated miRNAs-mRNAs changes associated with the onset of leukoaraiosis were involved in neurogenesis, neuronal development, and differentiation. Taken together, the study identified a set of candidate microRNA biomarkers that may usefully monitor the onset and progression of leukoaraiosis. Given the enrichment of leukoaraiosis-associated microRNAs and mRNAs in neuron part and membrane system, BAIAP3 could potentially represent a novel target of hsa-miR-1972 in leukoaraiosis through which microRNAs are involved in the pathogenesis of white matter lesions.

Ischemic stroke is the most common neurological disease. Previous researches have proven that ischemic lesion topography in specific brain structural regions and vascular territories are critical for outcome prediction and personalized treatment plan making. Compared to traditional two-dimensional visualization, computerized three-dimensional visualization provides more complete and interactive information regarding the ischemic lesion topography. In this paper, we propose a fast-processing pipeline for three-dimensional visualization of ischemic lesion topography. The pipeline is able to achieve in average 80.3% similarity with the traditional pipeline in terms of dice score while greatly shorten the processing time.

Familial Alzheimer's disease (FAD) present as a positive family history of cognitive decline, with early onset and an autosomal dominant inheritance pattern. FAD is mainly caused by the mutations in the genes encoding for amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2). In the present study, we identified a variant (c.529T > G, p.Phe177Val) in PSEN1 across three generations in a Chinese family with FAD using whole-exome sequencing. The mean age of onset was 39 years (range: 37 to 40 years) in this family. In cell transfection studies, the mutant PSEN1 protein carrying p.Phe177Val increased both the production of Aβ42 and the ratio of Aβ42 over Aβ40, as compared to wild-type PSEN1. Our results confirm the pathogenicity of PSEN1 p.Phe177Val variant in FAD and broaden the clinical phenotype spectrum of FAD patients with PSEN1 p.Phe177Val variant.