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Traditional recommender systems often suffer from the problem of data sparsity, because most users rate only a few of the millions of possible items. With the development of social platforms, incorporating abundant social relationships into recommenders can help to overcome this issue, because users' preferences can be inferred from those of their friends. Most existing social recommenders are based on matrix factorization, a collaborative filtering model that has been proven to be effective. In this paper, we introduce a novel social recommender based on the idea that distance reflects likability. Compared with matrix factorization, the proposed model enables us to obtain a spatial understanding of the latent factor space and how users and items are positioned inside the space by combining the factorization model and distance metric learning. In our method, users and items are initially mapped into a unified low-dimensional space. The positions of users and items are jointly determined by ratings and social relations, which can help to determine appropriate locations for users who have few ratings. Finally, the learned metrics and positions are used to generate understandable and reliable recommendations. Experiments conducted on real-world data sets have shown that compared with methods based on only matrix factorization, our method significantly improves the recommendation accuracy.

Gas diffusion layers (GDLs) play a significant role in the efficient operation of high-temperature polymer electrolyte fuel cells. They connect the electrodes to the gas channels of the bipolar plate by porous material with a meso-scale geometric structure. The electrodes must be sufficiently supplied by gases from the channels to operate fuel cells efficiently. Furthermore, reaction products must be transported in the other direction. The gas transport is simulated in the through-plane direction of the GDL, and its microstructure created by a stochastic model is equivalent to the structure of real GDL material. Continuum approaches in cell-scale simulations have model parameters for porous regions that can be taken from effective properties calculated from the meso-scale simulation results, as one feature of multi-scale simulations. Another significant issue in multi-scale simulations is the interface between two regions. The focus is on the gas flow at the interface between GDL and the gas channel, which is analyzed using statistical methods. Quantitative relationships between functionality and microstructure can be detected. With this approach, virtual GDL materials can possibly be designed with improved transport properties. The evaluation of the surface flow with stochastic methods offers substantiated benefits that are suitable for connecting the meso-scale to larger spatial scales.

Abstract Depression is a mood disorder mainly clinically characterized by significant and persistent low spirits. Chronic stress is the leading cause of depression. However, traditional medicine has severe side effects in treating depression, ineffective treatment, and easy recurrence. Therefore, it is of great significance to prevent depression in the environment of chronic stress. In this study, aromatherapy was used for the prevention of depression. To solve the defects of intense volatility and inconvenience in using essential oils, we designed bionic nano-aromatic drugs and adhered them to the wallpaper. Inspired by the moldy wallpaper, we successively prepared the morphology-bionic nano-aromatic drugs, the function-bionic nano-aromatic drugs, and the bionic plus nano-aromatic drugs by referring to the morphology of microorganisms and substances in bacterial biofilms. Bionic nano-aromatic drugs remarkably promoted their adhesion on wallpaper. Molecular dynamics simulation explored its molecular mechanism. The essential oils, which were slowly released from the bionic nano-aromatic drugs, showed excellent biosecurity and depression prevention. These sustainedly released essential oils could significantly increase monoamine neurotransmitters in the brain under a chronic stress environment and had excellent neuroprotection. Besides, the bionic nano-aromatic drugs with simple preparation process and low cost had excellent application potential.

Abstract Objective This study aimed to explore the association between slow‐wave sleep and the progression of motor and nonmotor symptoms in patients with PD. Methods Data were collected from the Parkinson's Progression Markers Initiative study. Slow‐wave sleep, also known as deep non‐rapid eye movement (DNREM) sleep, was objectively assessed using the Verily Study Watch. Motor function was assessed using the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale Part III score, Hoehn and Yahr stage, freezing of gait, motor fluctuations, and dyskinesia severity. Comprehensive assessments were conducted on nonmotor symptoms, including depression, anxiety, global cognitive function, and autonomic dysfunction. Statistical analyses involved repeated‐measures analysis of variance and linear regression. Results A total of 102 patients with PD were included in the study, with a median follow‐up duration of 3.4 years. In the long DNREM sleep duration group (n = 55), better motor function (DNREM × time interaction: F(1,100) = 4.866, p = 0.030), less severe sexual dysfunction (p = 0.026), and improved activities of daily living (p = 0.033) were observed at the last follow‐up visit compared with the short DNREM sleep duration group (n = 47). Reduced DNREM sleep duration is a risk factor for motor progression (β = −0.251, p = 0.021; 95% confidence interval = −0.465 to −0.038). Interpretation The findings suggest an association between longer DNREM sleep duration and slower motor and nonmotor progression in patients with PD.

Reactive oxygen species (ROS)-mediated oxidative stress exacerbates chronic diseases such as organ damage and neurodegenerative disorders. The Keap1-Nrf2-ARE pathway is a widely distributed endogenous antioxidant system. However, ROS under redox homeostasis regulates a wide range of life activities. Therefore, smart scavenging of excess ROS under pathological conditions is essential to treat chronic diseases safely. This study reports a smart antioxidant function enhancement (SAFE) strategy. On-demand release of nucleic acid drugs in a pathological ROS environment smartly activates the endogenous antioxidant system, thereby smartly alleviating oxidative stress in an exogenous antioxidant-independent manner. Through structural modulation and ligand modification, we develop SAFE nanoparticles based on nanohybrid complexes (SAFE-complex) adapted to brain delivery of nucleic acid drugs. SAFE-complex with homogeneous monodisperse structure efficiently treat ROS-related neurodegenerative diseases while protecting the major organ from oxidative stress damage. Moreover, SAFE-complex can stabilize storage in the form of freeze-dried powder. These data indicate that SAFE nanoparticles hold promise for treating ROS-related chronic diseases and comorbidities through rational transformation.

Abstract Objectives To compare the long‐term safety and efficacy of stenting in correcting cerebral venous sinus stenosis (CVSS) and internal jugular venous stenosis (IJVS). Methods Patients confirmed with CVSS or IJVS by imaging were enrolled in this real‐world study from 2014 through 2021. Clinical characteristics and long‐term outcomes of these two diseases entities post‐stenting were followed up and compared. Results Three hundred and nineteen patients were enrolled in this study, with a mean age of 48.83 years and a BMI of 25.08 on average. In which, 144 patients underwent stenting, the stenotic segments were corrected and the venous blood flow was restored immediately post‐stenting. At 6.15 ± 1.67 days follow‐up, significant improvement was observed in headache, tinnitus, insomnia, ICP, and mean pressure gradient in both groups (all p

Background: The coronavirus disease-2019 (COVID-19) pandemic worldwide has caused a high burden of mental problems, which may be associated with subjective cognitive impairment in the general population. Objectives: This cross-sectional survey aimed to investigate the level and pattern of cognitive failure (CF) and its negative changes during the COVID-19 pandemic among the general population in China. Methods: The participants completed an online questionnaire between April 18 and May 4, 2020, and those aged between 18 and 70 were included in this study. CF was measured using the 14-item CF Questionnaire (CFQ-14). Factors associated with CF and negative changes in CF were evaluated using multiple linear and logistic regression models. A total of 30,879 eligible participants were recruited; most were female (59.10%) and aged 31–45 (61.51%). Results: The mean CFQ-14 score was 15.62 (standard deviation = 11.55), and 4,619 (14.96%) participants reported negative changes in CF during the pandemic. Multiple regression analyses showed that participants with female gender, history of physical and mental disease, the self-perceived influence of COVID-19, altered appetite and taste preference, worse interpersonal relationships, long sleep duration, poor sleep quality, depressive, anxiety and posttraumatic stress disorder symptoms had a higher level of CF and negative CF changes, while regular exercise was associated with a lower risk of both outcomes. Conclusions: This study indicates that CF symptoms should be monitored in the general population during pandemics. A healthy lifestyle and reduction in psychological stress could help promote normal cognitive function during pandemics.

Highlights There are significant sex differences in Chinese population with cognitive impairment in Lewy body disease. Women were more common in dementia with Lewy bodies and mild cognitive impairment with Lewy bodies cases, had more frequent and severe neuropsychiatric symptoms, and poorer cognition than men. Men predominant in Parkinson’s disease with mild cognitive impairment and Parkinson’s disease with dementia cases, and performed more frequent RBD and parkinsonism than women. Dementia with Lewy bodies vs. Parkinson’s disease with dementia, and mild cognitive impairment with Lewy bodies vs. Parkinson’s disease with mild cognitive impairment are distinct disease forms and should not be confused.

BackgroundThe clinical features and pathological process of cerebral microbleed (CMB)-related cognitive impairment are hot topics of cerebral small vessel disease (CSVD). However, how to choose a more suitable cognitive assessment battery for CMB patients is still an urgent issue to be solved. This study aimed to analyze the performance of CMB patients on different cognitive tests.MethodsThis study was designed as a cross-sectional study. The five main markers of CSVD (including the CMB, white matter hyperintensities, perivascular spaces, lacunes and brain atrophy) were assessed according to magnetic resonance imaging. The burden of CMB was categorized into four grades based on the total number of lesions. Cognitive function was assessed by Mini-Mental State Examination (MMSE), Trail-Making Test (TMT, Part A and Part B), Stroop color-word test (Stroop test, Part A, B and C), Verbal Fluency Test (VF, animal), Digit-Symbol Substitution Test (DSST), Digit Cancellation Test (DCT) and Maze. Multiple linear regression analysis was conducted to analyze the association between CMB and cognitive findings.ResultsA total of 563 participants (median age of 69 years) were enrolled in this study, including 218 (38.7%) CMB patients. CMB patients showed worse performance than non-CMB subjects in each cognitive test. Correlation analysis indicated the total number of CMB lesions had positive correlations with the time of TMT, Maze and Stroop test, and negative correlations with the performance of MMSE, VF, DSST, and DCT. After the adjustment for all the potential confounders by linear regression, the CMB burden grade was correlated with the performance of VF, Stroop test C, Maze and DCT.ConclusionThe presence of CMB lesions was associated with much worse cognitive performances. In VF, Stroop test C, Maze and DCT, the correlations between CMB severity and assessment results were more significant. Our study further confirmed that the attention/executive function domain was the most commonly evaluated in CMB, which provided a picture of the most utilized tools to analyze the prognostic and diagnostic value in CMB.

Offshore oil and gas production has become an important growth pole to ensure national energy security. However, China's offshore oil and gas production is lack of key core technologies and weak in tool and equipment foundation and can hardly support the optimized fast development of important fields. To solve these technological difficulties, China National Offshore Oil Corporation (CNOOC) insisted on independent technological innovation and overcame a series of key core technologies through theoretical research and key technology research and test during the 13th Five-Year Plan. And the following research results are obtained. First, several key technologies are broken through, including efficient drilling and completion in the middle and deep layers of the Bohai Sea, offshore large-scale heavy oil thermal recovery, deep-water oil and gas field development, and high temperature and high pressure well drilling and completion in the South China Sea, unconventional oil and gas stimulation, and offshore emergency rescue. Domestic first independently operated ultra deep water giant gas field, namely “Deepsea 1” is successfully put into production, so that the leap from 300 m to 1500 m of water depth and from exploration to development is realized. Second, key tools and equipment are developed, such as logging while drilling and rotary steering drilling system, deep-water drilling surface conductor, underwater emergency killing device, and underwater wellhead Christmas tree, which promote the high-quality development of China's offshore oil industry. Finally, some suggestions are proposed as follows. In the future, CNOOC shall strengthen independent technological innovation, quicken the pace to deepsea oil and gas, and continue to research key core technologies for oil and gas reserves and production increase (e.g. continuous localization of drilling and completion technologies, equipment and materials in complex fields), commingled gas production and test and green energy transformation (e.g. geothermal energy), so as to make greater contributions to ensure national energy security and build a maritime power.

Background and objectiveCognitive impairment (CI) is a substantial contributor to the disability associated with Parkinson’s disease (PD). We aimed to assess the clinical features and explore the underlying biomarkers as predictors of CI in patients with newly diagnosed PD (NDPD; less than 2 years).MethodsWe evaluated the cognitive function status using the Montreal Cognitive Assessment (MoCA) and a battery of neuropsychological tests at baseline and subsequent annual follow-up for 5 years from the Parkinson’s Progression Markers Initiative (PPMI) database. We assessed the baseline clinical features, apolipoprotein (APO) E status, β-glucocerebrosidase (GBA) mutation status, cerebrospinal fluid findings, and dopamine transporter imaging results. Using a diagnosis of CI (combined mild cognitive impairment and dementia) developed during the 5-year follow-up as outcome measures, we assessed the predictive values of baseline clinical variables and biomarkers. We also constructed a predictive model for the diagnosis of CI using logistic regression analysis.ResultsA total of 409 patients with NDPD with 5-year follow-up were enrolled, 232 with normal cognitive function at baseline, and 94 patients developed CI during the 5-year follow-up. In multivariate analyses, age, current diagnosis of hypertension, baseline MoCA scores, Movement disorder society Unified PD Rating Scale part III (MDS-UPDRS III) scores, and APOE status were associated with the development of CI. Predictive accuracy of CI using age alone improved by the addition of clinical variables and biomarkers (current diagnosis of hypertension, baseline MoCA scores, and MDS-UPDRS III scores, APOE status; AUC 0.80 [95% CI 0.74–0.86] vs. 0.71 [0.64–0.77], p = 0.008). Cognitive domains that had higher frequencies of impairment were found in verbal memory (12.6 vs. 16.8%) and attention/processing speed (12.7 vs. 16.9%), however, no significant difference in the prevalence of CI at annual follow-up was found during the 5-year follow-up in NDPD patients.ConclusionIn NDPD, the development of CI during the 5-year follow-up can be predicted with good accuracy using a model combining age, current diagnosis of hypertension, baseline MoCA scores, MDS-UPDRS III scores, and APOE status. Our study underscores the need for the earlier identification of CI in NDPD patients in our clinical practice.

BackgroundAlcohol dependence (AD) remains one of the major public health concerns. Impulsivity plays a central role in the transfer from recreational alcohol use to dependence and relapse. White matter dysfunction has been implicated in alcohol addiction behaviors and impulsivity. However, little is known about the role of systematic striatal structural connections underlying the mechanism of impulsive traits in AD.MethodsIn our study, we used seed-based classification by probabilistic tractography with five target masks of striatal circuits to explore the differences in white matter integrity (fractional anisotropy, FA) in AD male patients (N = 51) and healthy controls (N = 27). We mainly explored the correlation between FA of the striatal circuits and impulsive traits (Barratt Impulsiveness Scale, BIS-11), and the mediation role of impulsivity in white matter integrity and the severity of alcohol dependence.ResultsCompared with healthy controls, AD showed much lower FA in the left and right striatum–supplementary motor area (SMA) and left striatum–amygdala. We also found the decreased FA of right striatum-vlPFC was correlated with higher impulsivity. Besides, the relationship between reduced FA of right striatum-vlPFC and severity of dependence could be mediated by impulsivity.ConclusionIn our study, we found disrupted white matter integrity in systematic striatal circuits in AD and the decreased FA of right striatum-vlPFC was correlated with higher impulsivity in AD. Our main findings provide evidence for reduced white matter integrity of systematic striatal circuits and the underlying mechanisms of impulsivity in male AD individuals.

Abstract Background Lewy body dementia (LBD), consisting of dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), is the second most common type of neurodegenerative dementia in older people. The current study aimed to investigate the clinical characteristics of LBD in Chinese memory clinics. Methods A total of 8405 dementia medical records were reviewed, revealing 455 patients with LBD. Demographic data, neuropsychological scores, and the scale for Medial Temporal lobe Atrophy (MTA) were then analyzed from nine memory clinics in the China Lewy Body Disease Collaborative Alliance. Results The clinical proportion of LBD among the subjects and among all dementia types was 5.4% (4.9–5.9%) and 7.3% (6.7–8.0%), respectively, with a mean onset age of 68.6 ± 8.4 years. Patients with DLB comprised 5.6% (n = 348, age of onset 69.1 ± 8.3), while PDD comprised 1.7% (n = 107, age of onset 66.7 ± 8.8) of all dementia cases. There were slightly more males than females with DLB (n = 177, 50.9%) and PDD (n = 62, 57.9%). Patients with DLB had a poorer performance compared to those with PDD on the MMSE (16.8 ± 7.1 vs. 19.5 ± 5.7, p = 0.001), the MoCA (11.4 ± 6.6 vs. 14.0 ± 5.8, p

IntroductionThe exact relationship between long-term shift work (SW) and cognitive impairment (CI) has been poorly understood. The effects of the long-term rotating night SW (RNSW) combining daytime recharge (DTR) on cognitive function were investigated.MethodsA total 920 retired nurses and 656 retired female teachers aged ≥50 years were analyzed. Participants who worked at least once per week for 8 hat night for more than 1 year were defined as the SW group, and those without a regular nighttime shift were defined as the control group. The associations among duration, frequency, and DTR of RNSW, and neuropsychological assessments were ascertained by regression models.ResultsParticipants with RNSW had a significantly higher proportion of mild CI (MCI), both amnestic MCI (aMCI) (14.4% in 11–20 years, p < 0.05, and 17.8% in > 20 years, p < 0.001) and non-amnestic MCI (naMCI) (8.1% in 11–20 years, p < 0.05), as well as dementia (1.5% in 1–10 years, and 11.7% in > 20 years, p < 0.05) compared to controls (8.4% with aMCI, 4.4% with naMCI, and 7.0% with dementia, respectively). There were significant negative relationships between general times of night SW and scores of Mini-Mental State Examination (MMSE) (R squared = 0.01, p = 0.0014) and Montreal Cognitive Assessment (MoCA) (R squared = 0.01, p = 0.0054). Participants with ≥1 h of DTR and ≥ 11 years of RNSW were about 2-fold more likely to experience MCI compared with the subjects in the control group, especially with 3–5 h (odds ratio [OR]: 2.35; 95% confidence interval: 1.49–3.68, p < 0.001).ConclusionThe long-term RNSW was associated with a higher risk of CI, especially aMCI and dementia, and the problem cannot be improved by DTR.

Abstract Background The modified Rankin Scale (mRS) is a key global outcome measure after stroke internationally. The latest English version of the simplified modified Rankin scale questionnaire (smRSq)(2011) is a reliable and valid tool in scoring the mRS after stroke. In order to use this tool in Chinese patients, we translated it into Chinese and tested its clinimetric properties. Methods The English version smRSq (2011) was translated into Chinese by a standard process. We recruited 300 consecutive hospitalized ischemic stroke patients in the department of neurology, Beijing Chaoyang Hospital. Six randomly paired raters scored the conventional mRS, the novel Chinese version smRSq (2011), the National Institutes of Health Stroke Scale (NIHSS), and the Barthel index (BI) in-person. Inter-rater reliability and validity were assessed. Results Among the 300 ischemic stroke patients, mean age was 64.9 ± 12.1 years, and 220 (73%) were male. For inter-rater reliability of the smRSq (2011), the percent agreement among the paired raters was 87%, the kappa (κ) was 0.84 (95% CI, 0.79–0.88), and the weighted kappa (κw) was 0.96 (95% CI, 0.95–0.98). The percent agreement between the smRSq (2011) scores and the conventional mRS scores was 55%, κ = 0.47 (95% CI, 0.40–0.54), and κw = 0.91 (95% CI, 0.89–0.93). In construct validity testing, the Spearman’s correlation coefficients comparing the smRSq (2011) scores with the NIHSS and the BI scores were 0.83 (P

Background: Postoperative cognitive dysfunction (POCD) is a common complication after surgery and anesthesia. In this study, we aimed to determine the neuroprotective mechanism of Sirtuin 3 (SIRT3) and propofol in POCD. Methods: The cognitive dysfunction models in C57BL/6J mice were induced and treated, then cognitive function of mice were tested using morris water maze and novel object recognition tests. Primary neurons were stimulated by lipopolysaccharide (LPS) to mimic neuroinflammation during POCD. Meanwhile, cells were treated with propofol. 3-methyladenine (3-MA) was administrated to inhibit autophagy in neurons. SIRT3 overexpression vector was constructed to upregulate SIRT3. Biomarker changes in inflammation, oxidative stress and autophagy were determined in vivo and in vitro. Results: Propofol enhanced the spatial cognitive ability and novel objective recognition of POCD mice. Inflammation and oxidative stress were observed in the hippocampus, which were inhibited by propofol treatment. During POCD, SIRT3 expression and autophagy in the hippocampus was decreased; propofol activated autophagy and upregulated SIRT3. In LPS-stimulated neurons, SIRT3 upregulation enhanced the anti-inflammation and anti-oxidative stress roles of propofol; SIRT3 elevated propofol-activated autophagy in neurons undergoing LPS administration. Moreover, 3-MA reversed propofol-induced biomarker changes in inflammation, oxidative stress and autophagy in LPS-stimulated neurons. In POCD mice, SIRT3 upregulation enhanced the cognitive function during propofol treatment; SIRT3 overexpression elevated the inhibitory role of propofol in inflammation, oxidative stress and autophagy. AMPK/mTOR pathway was activated in response to propofol treatment and SIRT3 enhanced the signaling activation. Conclusions: SIRT3 enhances the protective effect of propofol on POCD by triggering autophagy that eliminates oxidative stress and inhibits the production of pro-inflammatory cytokines.

Background and ObjectiveThe combination of neuroimaging and cognition characteristics may provide complementary information for early identification of mild cognitive impairment (MCI). This study aimed to establish the clinical relevance between cerebral small vessel disease (CSVD) burden and MCI and further explored the cognitive characteristics linked to CSVD applying a propensity score matching (PSM) approach.MethodsThe study was designed as a case–control study. All the subjects underwent the standard clinical assessments, neuropsychological testing battery (including global cognition, memory, executive function, and speed and motor control domains), and brain magnetic resonance imaging (MRI). A 1:2 nearest-neighbor matching approach without replacement was employed with a caliper of 0.15 in the PSM approach.ResultsA total of 84 MCI patients and 186 cognitively normal controls were included in this study. After PSM, 74 MCI patients and 129 controls were successfully matched, and the covariate imbalance was well eliminated. Compared with controls, the MCI group had more severe CSVD burden. In the binary logistic regression analysis, CSVD was associated with MCI after adjusting for all confounders. The results of multivariate linear regression analyses showed that higher total MRI CSVD burden was related to the deficit of cognitive performance in global cognition and three important cognitive domains after adjusting for all confounders.ConclusionCerebral small vessel disease was an independent risk factor of MCI. Moreover, higher total MRI CSVD burden was associated with the overall cognitive impairment among middle-aged and elderly Chinese adults.

Abstract Background The exact relationship between 25-hydroxyvitamin D [25(OH) D] levels and small vessel disease (SVD) are not clear in China. The aim of this study was to determine such the association between 25(OH) D and SVD in China. Methods We retrospectively enrolled 106 patients with SVD and 115 controls between Jan 2017 and Dec 2017. All the subjects were categorized into three subgroups according to the level of 25 (OH) D: vitamin D deficiency ( 20 ng/ml). Results Among 106 SVD patients, 80 (75.5%) were men and the mean age was 61.6 ± 13.2 years. The deficiency of 25(OH) D was observed in 76 (71.7%) of SVD patients and 47 (40.9%) of controls (P = 0.001). Compared with controls, patients with SVD were more likely to be male, a stroke history, smokers, with hyperlipidemia, higher systolic and diastolic blood pressure and low-density lipoprotein, and lower of 25(OH)D level (P

Abstract Background Anti leucine-rich glioma inactivated 1 (LGI1) encephalitis is a rare autoimmune encephalitis (AE), characterized by acute or subacute cognitive impairment, faciobrachial dystonic seizures, psychiatric disturbances and hyponatremia. Antibody-LGI 1 autoimmune encephalitis (anti-LGI1 AE) has increasingly been recognized as a primary autoimmune disorder with favorable prognosis and response to treatment. Case presentation Herein, we reported a male patient presenting as rapidly progressive dementia and hyponatremia. He had antibodies targeting LGI1 both in the cerebrospinal fluid and serum, which demonstrated the diagnosis of typical anti-LGI1 AE. The scores of Mini-Mental State Examination and Montreal Cognitive Assessment were 19/30 and 15/30, respectively. Cranial magnetic resonance images indicated hyperintensities in bilateral hippocampus. The findings of brain arterial spin labeling and Fluorine-18-fluorodeoxyglucose positron emission tomography showed no abnormal perfusion/metabolism. After the combined treatment of intravenous immunoglobulin and glucocorticoid, the patient’s clinical symptoms improved obviously. Conclusions This case raises the awareness that a rapid progressive dementia with predominant memory deficits could be induced by immunoreactions against LGI1. The better recognition will be great importance for the early diagnosis, essential treatment, even a better prognosis.

Neurodevelopmental and neurodegenerative diseases (NDDs) with severe neurological/psychiatric symptoms, such as cerebrovascular pathology in AD, CAA, and chronic stroke, have brought greater attention with their incidence and prevalence having markedly increased over the past few years. Causes of the significant neuropathologies, especially those observed in neurological diseases in the CNS, are commonly believed to involve multiple factors such as an age, a total environment, genetics, and an immunity contributing to their progression, neuronal, and vascular injuries. We primarily focused on the studies of glial involvement/dysfunction in part with the blood-brain barrier (BBB) and the neurovascular unit (NVU) changes, and the vascular mechanisms, which have been both suggested as critical roles in chronic stroke and many other NDDs. It has been noted that glial cells including astrocytes (which outnumber other cell types in the CNS) essentially contribute more to the BBB integrity, extracellular homeostasis, neurotransmitter release, regulation of neurogenic niches in response to neuroinflammatory stimulus, and synaptic plasticity. In a recent study for NDDs utilizing cellular and molecular biology and genetic and pharmacological tools, the role of reactive astrocytes (RACs) and gliosis was demonstrated, able to trigger pathophysiological/psychopathological detrimental changes during the disease progression. We speculate, in particular, the BBB, the NVU, and changes of the astrocytes (potentially different populations from the RACs) not only interfere with neuronal development and synaptogenesis, but also generate oxidative damages, contribute to beta-amyloid clearances and disrupted vasculature, as well as lead to neuroinflammatory disorders. During the past several decades, stem cell therapy has been investigated with a research focus to target related neuro-/vascular pathologies (cell replacement and repair) and neurological/psychiatric symptoms (paracrine protection and homeostasis). Evidence shows that transplantation of neurogenic or vasculogenic cells could be achieved to pursue differentiation and maturation within the diseased brains as expected. It would be hoped that, via regulating functions of astrocytes, astrocytic involvement, and modulation of the BBB, the NVU and astrocytes should be among major targets for therapeutics against NDDs pathogenesis by drug and cell-based therapies. The non-invasive strategies in combination with stem cell transplantation such as the well-tested intranasal deliveries for drug and stem cells by our and many other groups show great translational potentials in NDDs. Neuroimaging and clinically relevant analyzing tools need to be evaluated in various NDDs brains.

Drilling fluid loss in depleted reservoir has been an import issue faced by further tapping the potential of old oil fields. Accurate evaluation of the fracture pressure is the foundation to avoid mud loss. Traditional views suggest that tensile failure is the only fracture mode and the fracture pressure should be determined by a tensile failure criterion, which are not suitable for wells drilled in the depleted reservoir. In this paper, the analysis focuses on the fracture mode and fracture pressure in depleted reservoir, and case studies show that three fracture modes may first occur, and the fracture mode will be changed with reservoir depletion which highly depends on reservoir depletion degree, well azimuth and deviation angle, and the in situ stress state; different failure criteria at different stages of reservoir depletion should be selected to accurately evaluate the fracture pressure. For the vertical well, fracture pressure is no longer a single linear reduction with reservoir depletion; instead, a three-step and two-step reduction may appear, and for the directional well, the fracture pressure is not always decreased; the other patterns such as increase and first increase then decrease may also appear for the wells drilled in reverse and strike fault stress regimes.

Agenesis of the corpus callosum (AgCC) is a rare congenital malformation characterized by partial or complete absence of the corpus callosum (CC). The effects of AgCC on cerebral structural and functional networks are not clear. We aimed to utilize AgCC as a model to characterize the relationship between brain structure and function. Diffusion tensor imaging and resting-state fMRI data were collected from nine AgCC and ten healthy subjects. The interhemispheric functional connectivity (FC) was quantified using a voxel-mirrored-homotopic-connectivity (VMHC) method, and its correlation with the number (FN) and fractional anisotropy (FA) of the fibers crossing the CC was calculated. Graph-based network analyses of structural and functional topologic properties were performed. AgCC subjects showed markedly reduced VMHC compared to controls. VMHC was significantly correlated with the FN and FA of the fibers crossing the CC. Structural network analyses revealed impaired global properties, but intact local properties in AgCC compared to controls. Functional network analyses showed no significant difference in network properties between the groups. Finally, in both groups, brain areas with more fiber connections were more likely to build a positive FC with each other, while areas with decreased white matter connections were more likely to result in negative FC. Our observations demonstrate that interhemispheric FC is highly dependent on CC structure. Increased alternative intrahemispheric SC might be a compensatory mechanism in AgCC that helps to maintain normal global brain function. Our study provides insights into the underlying neurological pathophysiology of brain malformations, thereby helping to elucidate the structure–function relationship of normal human brain.

Abstract Background Whether there are differences in pathogenesis among different types and subtypes of cerebral watershed infarction (WSI) is controversial since they have been combined into a single group in most previous studies. Methods We prospectively identified 340 supratentorial WSI patients at Beijing Chao-Yang Hospital, Capital Medical University, China and classified them based on diffusion-weighted imaging(DWI) templates. Baseline characteristics, clinical courses and neuroradiological features were compared among patients with different types and subtypes of WSI. Results We identified 92 patients with cortical watershed infarction (CWI), 112 with internal watershed infarction (IWI) and 136 with mixed-type infarction. Compared with CWI patients, more IWI patients had critical stenosis of internal carotid artery (ICA) (P

Background: Recently, the [diagnosis of transient ischemic attack (TIA), DOT] score has been recognized to be a new tool for non-specialists to diagnose TIA more accurately with the sensitivity and specificity being 89 and 76%, respectively. However, the DOT score has not yet been validated externally in patients with TIA in China.Methods: We retrospectively enrolled 500 consecutive patients with transient neurological symptoms, who were admitted to the Department of Neurology, Beijing Chaoyang Hospital and underwent magnetic resonance imaging (MRI) between Jan 2016 and Dec 2018. Patients with transient neurological symptoms were divided into two subgroups: TIA mimic group (N = 140, 28%) and definite cerebrovascular events group including tissue-based TIA (DWI negative, N = 252, 50.4%) and minor stroke (DWI positive, N = 108, 21.6%). The demographic data, clinical characteristics, laboratory findings, and scores of Dawson and DOT were compared between the two groups.Results: A total of 500 patients with transient neurological symptoms (mean age, 61.1 ± 12.8) were enrolled and 70% (N = 350) were male. Comparing with TIA mimic groups, patients with cerebrovascular events group were more likely to have higher diastolic blood pressure, uric acid and homocysteine, more motor weakness and speech abnormalities, and also scored higher using the Dawson and DOT. The area under the curve (AUC) was 0.728 for DOT, with a sensitivity of 70.3% and specificity of 62.9%, respectively.Conclusion: In patients with transient neurological symptoms, our findings showed that the DOT score had relatively good calibration and discrimination to identify of TIA in a Chinese Population. As a novel tool of TIA identification, further validations are needed in multiple centers with larger samples in China.

Background: The associations between the clinical characteristics and diffusion-weighted imaging (DWI) positivity in patients with a clinical diagnosis of transient ischemic attack (TIA) are still poorly understood. The purpose of our study was to determine the incidence of TIA related acute infarction by DWI, and to determine the underlying predictors of DWI positivity in TIA patients.Methods: Between Jan 2017 and Dec 2018, we retrospectively enrolled 430 patients with a clinical diagnosis of TIA who underwent DWI. Patients were divided into those with acute ischemic lesions (DWI positive group) and those without (DWI negative group). The clinical characteristics, laboratory data, and imaging parameters were compared between the two groups.Results: A total of 430 time-based TIA patients (mean age, 61.4 ± 13.0) were enrolled in this study. About 126 (29.3%) of TIA patients had a DWI positive lesion in our series. Comparing TIA patients with positive DWI to those with negative DWI, acute lesions were more likely to be more male, have higher hyperlipidemia and a smoking history, more speech abnormalities and increased motor weakness; and higher systolic and diastolic blood pressure, homocysteine, fasting blood glucose, and the scores of ABCD2, ABCD3, ABCD3-I, and Dawson. Several independent predictors of DWI positivity were identified with logistic regression analysis: motor weakness (odds ratio 4.861, P = 0.021), speech abnormalities (odds ratio 4.029, P = 0.024), and ABCD3-I (odds ratio 13.141, P = 0.001). ABCD3-I showed the greatest area under the ROC curve, with a sensitivity of 85.7% and specificity of 72.4%.Conclusion: In patients with a clinical diagnosis of TIA, 29.3% demonstrated acute DWI lesions on brain magnetic resonance imaging (MRI). They were associated with motor weakness, speech abnormalities and higher ABCD3-I score at admission.

Accumulated data suggests that cerebral microbleeds (CMBs) play an important role in the decline of cognitive function, but the results remain inconsistent. In the current study, we aimed to investigate the association between CMBs and cognitive function, as well as the various effects of CMBs on different domains of cognition.We searched through the databases of PubMed, Embase, Cochrane Library, and ScienceDirect. After a consistency test, the publication bias was evaluated and a sensitivity analysis was performed with combined odds ratios (OR) and standardized mean difference (SMD) of CMBs.A meta-analysis of 25 studies with 9343 participants total was conducted. Patients with CMBs had higher incidence of cognitive impairment (OR:3.5410; 95% confidence interval [CI] [2.2979, 5.4567], p

Enlarged perivascular spaces (EPVS) correlate with cognitive impairment and incident dementia. However, etiologies for severe basal ganglia EPVS (BG-EPVS) are still unclear. Our aim was to investigate the independent risk factors for severe BG-EPVS in patients with acute lacunar stroke.We prospectively identified patients with lacunar stroke (diameter on DWI ≤ 20mm) from Jan 2011 to May 2015. Patients with severe BG-EPVS were identified on T2 weighted MRI. Age (± 1 year) and sex matched controls were also recruited in the same population (two controls for one case). Vascular risk factors, clinical data, EPVS in centrum semiovale (rated 0 to 4), white matter hyperintensities (WMH) (by Fazekas scale), brain atrophy (rated 0 to 6) were compared between two groups. Logistic regression was performed to determine independent risk factors for severe BG-EPVS.During study period, 89 patients with severe BG-EPVS and 178 matched controls were included. Vascular risk factors did not differ between two groups. Patients with severe BG-EPVS had lower level of HbA1c and diastolic BP at admission, but presented with larger infarct size, more severe WMH (including total WMH, periventricular WMH and deep WMH) and brain atrophy. In logistic regression, brain atrophy (OR = 1.40; 95%CI 1.13, 1.73) and deep WMH (OR = 1.88; 95%CI 1.24, 2.83) were independent risk factors for severe BG-EPVS.Brain atrophy and deep WMH are independent risk factors for severe BG-EPVS, supporting the hypothesis that brain atrophy may be associated with the development of EPVS in basal ganglia.

Severe stroke patients have poor clinical outcome which may be associated with development of multiple organ dysfunction syndrome (MODS). Therefore, the aim of our study was to investigate independent risk factors for development of MODS in severe stroke patients.Ninety seven severe stroke patients were prospective recruited from Jan 2011 to Jun 2015. The development of MODS was identified by Sequential Organ Failure Assessment (SOFA) score (score ≥ 3, at least two organs), which was assessed on day 1, 4, 7, 10 and 14 after admission. Baseline characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Glasgow coma score (GCS) and cerebral imaging parameters were collected at admission. Cox regression was performed to determine predictors for the development of MODS. Medical complications after admission and in-hospital mortality were also investigated.33 (34%) patients were in MODS group and 64 (66%) were in non-MODS group within 14 days after admission. Patients in MODS group had more smoker (51.5% vs 28.1%, p = 0.023), higher NIHSS score (23.48 ± 6.12 vs 19.81 ± 4.83, p = 0.004), higher APACHE II score (18.70 ± 5.18 vs 15.64 ± 4.36, p = 0.003) and lower GCS score (6.33 ± 2.48 vs 8.14 ± 2.73, p = 0.002). They also had higher rate of infarction in multi vascular territories (36.4% vs 10.9%, p = 0.003). The most common complication in all patients was pulmonary infection, while complication scores were comparable between two groups. Patients with MODS had higher in-hospital mortality (69.7% vs 9.4%, p = 0.000). In Cox regression, NIHSS score (RR = 1.084, 95% CI 1.019-1.153) and infarction in multi vascular territories (RR = 2.345 95% CI 1.105-4.978) were independent risk factors for development of MODS.In acute phase of stroke, NIHSS score and infarction in multi vascular territories predicted MODS in severe stroke patients. Moreover, patients with MODS had higher in-hospital mortality, suggesting that early identification of MODS is critical important.

Jie Yu Chu Fan capsule (JYCF) is a new compounded Chinese herbal medicine for the treatment of depression. The present study was designed to explore the antidepressant effects and the possible mechanisms of JYCF by using chronic unpredictable mild stress (CUMS) mouse model and comparing results to that of fluoxetine. Behavioral tests including an open field test, sucrose preference test and forced swim test were performed to evaluate the antidepressant effects of JYCF. The concentrations of monoamine neurotransmitters and metabolic products including norepinephrine (NE), 5-hydroxytryptamine (5-HT), dopamine (DA), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the cerebral cortex and hippocampus of mice were determined by means of high performance liquid chromatography with electrochemical detection (HPLC-EC). The results show that a successful mouse CUMS model was established through 5 weeks of continuous unpredictable stimulation, as indicated by the significant decrease in sucrose preference and locomotor activity and increase in immobility time in the forced swim test. Chronic treatment of JYCF (1.25, 2.5 and 5 g/kg) and fluoxetine (20 mg/kg) significantly reversed the CUMS-induced behavioral abnormalities. JYCF (1.25, 2.5 and 5 g/kg) significantly increased NE in CUMS mouse prefrontal cortex (P < 0.01, P < 0.01, P < 0.05 respectively) and 5-HT in hippocampus (P < 0.05). In summary, our findings suggest that JYCF exerts comparable antidepressant-like effects to that of fluoxetine in CUMS mice. Besides, the antidepressant-like effect of JYCF is mediated by the increase of monoaminergic transmitters including 5-HT and NE.