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Rapid urbanization has led to ecological destruction and associated issues. Macro policies wield substantial influence over urbanization and its relationship with the environment. Without considering the differences in scale, macro policies may be ineffective at addressing urbanization's adverse impacts on the environment, and even worsen this relationship. We used data on 622 counties, 76 prefectures, and 7 urban agglomerations in the Yellow River Basin to examine the development level, coupling coordination degree, and spatial patterns of urbanization and ecosystem services at three scales during 2000-2020. Further, we explored the driving mechanisms in the relationship between urbanization and ecosystem services. We found that: First, the coupling coordination was relatively low but showed an upward trend. A sizeable spatiotemporal difference existed, with higher (lower) coordination in the east (west). Second, the coupling coordination of each scale exhibited significant spatial positive correlations. The low-value heterogeneous region was embedded around the agglomeration region, and polarization was significant. The larger the scale, the stronger the agglomeration effect. Further, the coupling coordination spatial agglomeration effect of each scale gradually weakened over time. Third, the spatial and temporal distributions of coupling coordination and its agglomeration characteristics at different scales differed. The urban agglomeration scale showed significant overall coordination or agglomeration characteristics, and prefecture and county regions showed local and unique characteristics within urban agglomerations. Fourth, the dominant factors influencing the spatial patterns of the coupling coordination at the county, prefecture, and urban agglomeration scales differed. The interaction and factor detection showed linear and double-factor enhancements. We find that economic development, government policies, environmental protection, and natural factors are the combined effects of urbanization and ecosystem services. Our research method can provide a reference for other river basins, and the results can help governments in formulating policies for sustainable development at different spatial scales.

The China’s economy is developing rapidly, and it affects the environment on several levels. Therefore, this study examines the effect of environmental management accounting, green human resource management (HRM), on green organisational behaviour (OB). We collected 383 questionnaires completed by human resource managers and accounting managers in the Chinese hospitality industry. We used a covariance-based structural equation model to test the hypotheses in this study. The empirical evidence shows a positive and significant effect between environmental management accounting (monetary environmental management accounting, and physical environmental management accounting) and green HRM (β = 0.262, p < 0.01, β = 0.378, p< 0.01). Green HRM mediates the influence of environmental management accounting (monetary environmental management accounting, β = 0.059, p < 0.01; physical environmental management accounting, β = 0.084, p< 0.01) on green OB. The analysis confirmed the importance of environmental management accounting (as opposed to green human resource management) in predicting green behaviour and the critical role of green human resource management in connecting environmental management accounting and green OB. Thus, this study extends the literature’s perspective on green OB to environmental management accounting and green HRM.

Objective This study investigates the differential expression and the mechanism of long intergenic non-protein coding RNA (LINC) 01857 in hepatocellular carcinoma (HCC) proliferation and apoptosis. Methods LINC01857 expression in HCC tissues and cells was evaluated. In addition, gain-of and loss-of functions were carried out to assess HCC cell proliferation and apoptosis. After that, LINC01857 subcellular localization was predicted and verified. Additionally, the binding relations between LINC01857 and microRNA (miRNA)-197-3p and between miR-197-3p and anterior GRadient 2 (AGR2) were detected and confirmed. Besides, HCC cell proliferation and apoptosis were assessed after silencing LINC01857 or overexpressing AGR2. Next, levels of key factors in the AKT and ERK pathways were measured. Additionally, xenograft transplantation was also conducted to confirm the effect of LINC01857 in HCC. Results LINC01857 was overexpressed in HCC. Silencing LINC01857 leads to a blockage in HCC cell proliferation but improved apoptosis. LINC01857 could competitively bind to miR-197-3p and thus upregulate AGR2. miR-197-3p was poorly expressed in HCC, while AGR2 was overexpressed. Mechanistically, downregulated miR-197-3p or overexpressed AGR2 were observed to attenuate the effect of the LINC01857 knockdown on suppressing cell proliferation and enhancing apoptosis. Moreover, LINC01857 activated the AKT and ERK pathways through the manipulation of the miR-197-3p/AGR2 axis in HCC. Conclusion The results of this study indicated that LINC01857 was highly expressed in HCC, and it could improve HCC cell proliferation and reduce apoptosis via competitively binding to miR-197-3p, promoting AGR2 and upregulating the AKT and ERK pathways.

TRIM59 is a protein that is highly expressed in a variety of tumors and promotes tumor development. However, the use of TRIM59 as tumor diagnosis and prognosis biomarker has not been fully explored. We collected datasets from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) to investigate its potential as a biomarker for diagnosis and prognosis. A total of 46 studies, including 11,558 patients were included in this study. Here, we showed that TRIM59 was significantly upregulated in 15 type of human solid tumors in comparison to their adjacent tissues. Receiver operating characteristic curve (ROC) results provided further evidence for the use of TRIM59 as a potential tumor diagnosis biomarker. Overall survival (OS) was compared between TRIM59 high expression and low expression groups. High expression of TRIM59 indicated a poor prognosis in multiple solid tumors. Taken together, these analyses showed that TRIM59 was upregulated in various types of tumors and had the potential to be used as a diagnostic and prognostic biomarker in human solid tumors.

This research explores and explains the path of family enterprise venture capital equity financing from the perspective of endogenous family control rights. We adopted unbalanced panel data on Chinese listed companies from 2007 to 2018. Empirical research shows that there are significant differences in the impact of venture capital on the growth performance of family enterprises and non-family enterprises. Venture capital negatively affects the growth performance of family enterprises, while the negative impact of venture capital on family enterprises is not significant. In addition, family control positively moderates the negative impact of venture capital on family enterprise growth performance.

BACKGROUND:Only a very few studies had compared the differences in topographic patterns of cerebral infarcts between middle cerebral artery (MCA) and internal carotid artery (ICA) disease. Besides, the comparison of clinical features and outcomes between MCA and ICA disease had rarely been reported. OBJECTIVES:To compare the clinical, imaging features and outcome of MCA versus ICA disease. METHODS:We prospectively enrolled 1172 patients with noncardiogenic ischemic stroke in ipsilateral ICA or MCA territory. Clinical, neuroradiologic and outcome of the two groups were compared in this observational cohort study. RESULTS:The ICA group more frequently presented with decreased alertness, gaze palsy, aphasia, and neglect than the MCA group at admission, and more often had higher National Institute of Health stroke scale score at admission and discharge. Meanwhile, the ICA group more frequently had multiple acute infarcts, watershed infarcts, territorial infarct, small cortical infarct, and responsible artery stenosis ≥70%. Whereas penetrating artery infarct and parent artery occluding penetrating artery was more often associated with MCA disease. The ICA group more frequently had inhospital complications of pneumonia and deep vein thrombosis, more often had disability at discharge, and had more recurrent ischemic stroke or transient ischemic attack in 1 Year. Multivariable logistic regression identified male (OR, 1.99; 95% CI, 1.30 to 3.05; P = 0.002), history of coronary heart disease (OR, 1.85; 95% CI, 1.03 to 3.32; P = 0.041), multiple acute infarcts (OR, 4.18; 95% CI, 2.07 to 8.45; P

BACKGROUND:Striae gravidarum is a common skin problem of considerable cosmetic concern for many pregnant women. Various risk factors associated with the development of striae have been reported, with conflicting results. OBJECTIVES:To analyze the risk factors of striae gravidarum in Chinese primiparous women and to provide evidence relevant to the prevention of this condition. METHODS:Singleton primiparous pregnant women who were hospitalized for delivery were included, and relevant data were collected. Independent risk factors associated with striae gravidarum in women with and those without striae gravidarum were identified using logistic regression. RESULTS:Among 213 singleton primiparous pregnant women, 125 had striae gravidarum, yielding a prevalence of up to 58.9%. There was a significant variation (P < 0.05, odds ratio >1) between the striae gravidarum and non-striae gravidarum groups in terms of several factors, including younger maternal age, weight gain during pregnancy, body mass index gain, uterine height, abdominal girth, and positive family history. Factors such as maternal height, birth weight, systemic disease, skin type, and neonatal gender did not significantly differ between the 2 groups. CONCLUSION:This study showed that the independent risk factors for striae gravidarum in primiparous women were younger maternal age, weight gain during pregnancy, body mass index gain, uterine height, abdominal girth, and a positive family history. The severity of striae gravidarum was associated with weight gain during pregnancy, body mass index gain, abdominal girth, and timing of the onset of striae gravidarum.

It is unclear in Chinese patients with acute stroke how the SOAR (stroke subtype, Oxfordshire Community Stroke Project classification, age, and prestrike modified Rankin) and mSOAR (modified-SOAR) scores performed in predicting discharge mortality and 3-month mortality. We aimed to validate the predictability of these scores in this cohort.Data from the China National Stroke Registry (CNSR) study was used to perform the mSOAR and SOAR scores for predicting the discharge and 3-month mortality in acute stroke patients.A total of 11073 acute stroke patients were included in present study. The increased mSOAR and SOAR scores were closely related to higher death risk in acute stroke patients. For discharge mortality, the area under the receiver-operator curve (AUC) of the mSOAR and SOAR scores were 0.784 (95% CI 0.761-0.807) and 0.722 (95% CI: 0.698-0.746). For 3-month mortality, they were 0.787 (95% CI: 0.771-0.803) and 0.704 (95% CI: 0.687-0.721), respectively. The mSOAR and SOAR scores showed significant correlation between the predicted and observed probabilities of discharge mortality (mSOAR: r = 0.945, P = 0.001; SOAR: r = 0.994, P

A newly assay, up-converting phosphor technology-based lateral flow (UPT-LF) assay, was developed for rapid and quantitative detection of N-terminal fragment of B-type natriuretic peptide precursor (NT-proBNP), one of the most important serum molecular maker of heat failure, in plasma samples as a point of care testing (POCT) method for diagnosis of acute heart failure. Human plasma from 197 patients with acute heart failure and 200 healthy controls was assessed using the UPT-LF assay, in a comparison with a Roche Elecsys assay. The limit of detection of the UPT-LF assay, with a coefficient of variation (CV) of less than 15%, was 116 ng/L, which is lower than the clinical diagnosis cutoff (150 ng/mL). The linear range was 50-35,000 ng/L. The CVs were less than 10% for both UPT-LF and Roche Elecsys assays for plasma samples under different storages, demonstrating the good stability and reproducibility. There are certain linear correlations between the results of UPT-LF and Roche Elecsys assay for EDTA-K2 and heparin-anticoagulated plasma, as well as for serum samples. For UPT-LF assay, there is a significant correlation between the values derived from analysis of EDTA-K2 and heparin-anticoagulated plasma samples (R = 0.995). No statistically significant difference was found between serum and plasma samples for UPT-LF assay. Our results demonstrate that NT-proBNP levels in healthy adults are elevated with age and had a relationship with sex, and with the age increase the NT-proBNP levels of females are significantly higher than those of males (p

To investigate the impact of low socioeconomic status (SES), indicated by low level of education, occupation and income, on 3 months functional outcome after ischemic stroke.We analyzed data from the China National Stroke Registry (CNSR), a multicenter and prospective registry of consecutive patients with acute cerebrovascular events occurred between September 2007 and August 2008. 11226 patients with ischemic stroke had SES and clinical characteristics data collected at baseline and mRS measured as indicator of functional outcome in 3 months follow up. Multinomial and ordinal logistic regression models were performed to examine associations between SES and the functional outcome.At 3 months after stroke, 5.3% of total patients had mRS scored at 5, 11.3% at score 4, 11.1% at score 3, 14.4% at score 2, 34.2% at score 1 and 23.7% at score 0. Compared to patients with educational level of ≥ 6 years and non-manual laboring, those < 6 years and manual laboring tended to have higher mRS score (P

A case-mix adjustment model has been developed and externally validated, demonstrating promise. However, the model has not been thoroughly tested among populations in China. In our study, we evaluated the performance of the model in Chinese patients with acute stroke.The case-mix adjustment model A includes items on age, presence of atrial fibrillation on admission, National Institutes of Health Stroke Severity Scale (NIHSS) score on admission, and stroke type. Model B is similar to Model A but includes only the consciousness component of the NIHSS score. Both model A and B were evaluated to predict 30-day mortality rates in 13,948 patients with acute stroke from the China National Stroke Registry. The discrimination of the models was quantified by c-statistic. Calibration was assessed using Pearson's correlation coefficient.The c-statistic of model A in our external validation cohort was 0.80 (95% confidence interval, 0.79-0.82), and the c-statistic of model B was 0.82 (95% confidence interval, 0.81-0.84). Excellent calibration was reported in the two models with Pearson's correlation coefficient (0.892 for model A, p

Aspiration after stroke has been associated with aspiration pneumonia, which contributes to increased mortality of stroke. Laryngeal elevation is a core mechanism for protection from aspiration. Few studies have explored the predictive value of laryngeal elevation velocity for aspiration after stroke. This study aimed to explore the ability of laryngeal elevation velocity to predict aspiration in patients with acute ischemic stroke.This was a prospective cohort study that included consecutive acute ischemic stroke patients treated at a teaching hospital during a 10-month period. Patients underwent magnetic resonance imaging (MRI) to confirm the diagnosis of acute ischemic stroke. Patients who were at risk of aspiration and could swallow 5 ml of diluted barium (40%, w/v) for a videofluoroscopic swallowing (VFS) study were included. The association between abnormal indices in the oral and pharyngeal phase of the VFS study and aspiration was examined using univariate analyses. These indices included the lip closure, tongue movement and control, laryngeal elevation velocity and range, the latency of pharyngeal swallowing, pharyngeal transit time (PTT), abnormal epiglottis tilt, residual barium in the pharynx, and the duration of upper esophageal sphincter (UES) opening. The laryngeal elevation velocity (%/s) was calculated as the range of laryngeal elevation (%) from the resting position to the maximum superior position or to the position where the laryngeal vestibule is fully closed divided by the corresponding duration of laryngeal elevation. The range of laryngeal elevation (%) was the percentage calculated as the distance between the resting laryngeal position and the maximum superior excursion position or position where the laryngeal vestibule is fully closed divided by the distance between the resting laryngeal position and the lowest edge of the mandible. A logistic regression analysis was used to determine the predictive value for aspiration secondary to reduced laryngeal elevation velocity after adjusting for the effects of other indices. Intrarater and interrater reliability were calculated using Pearson's correlation coefficients.Data from 89 patients were analyzed. This cohort included 71 males and 18 females with a mean age of 59.31±11.46 years. The mean time from stroke onset to the VFS study was 3 days (1-7). Twenty one (23%) patients aspirated while swallowing 5 ml of diluted barium (40%, w/v). Aspiration was associated with age, the velocity (%/s) of laryngeal elevation and duration, delayed pharyngeal phase, pharyngeal transit time, abnormal epiglottic tilt, and invalid laryngeal elevation before true swallowing, and duration of upper esophageal sphincter (UES) opening. After adjusting for the effects of the indices mentioned above, logistic regression analysis revealed that a reduced of laryngeal elevation velocity before vestibule closure was predictive of aspiration independently (OR, 0.993; 95% CI, 0.987-1.000).Reduced laryngeal elevation velocity for laryngeal elevated to position where laryngeal vestibule is fully closed was an independent predictor of aspiration in patients with acute ischemic stroke. This may be related to a decreased contraction velocity of the muscles involved in hyolaryngeal elevation. Therapeutic methods aimed at improving laryngeal elevation velocity may decrease aspiration events and pneumonias after stroke.

The elastic properties of renal glomeruli and their capillaries permit them to maintain structural integrity in the presence of variable hemodynamic forces. Measured by micro-indentation, glomeruli have an elastic modulus (E, Young's modulus) of 2.1 kPa, and estimates from glomerular perfusion studies suggest that the E of glomeruli is between 2 and 4 kPa. F-actin depolymerization by latrunculin, inhibition of acto-myosin contractility by blebbistatin, reduction in ATP synthesis, and reduction of the affinity of adhesion proteins by EDTA reduced the glomerular E to 1.26, 1.7, 1.5, and 1.43 kPa, respectively. Actin filament stabilization with jasplakinolide and increasing integrin affinity with Mg2+ increased E to 2.65 and 2.87 kPa, respectively. Alterations in glomerular E are reflected in commensurate changes in F/G actin ratios. Disruption of vimentin intermediate filaments by withaferin A reduced E to 0.92 kPa. The E of decellularized glomeruli was 0.74 kPa, indicating that cellular components of glomeruli have dominant effects on their elasticity. The E of glomerular basement membranes measured by magnetic bead displacement was 2.4 kPa. Podocytes and mesangial cells grown on substrates with E values between 3 and 5 kPa had actin fibers and focal adhesions resembling those of podocytes in vivo. Renal ischemia and ischemia-reperfusion reduced the E of glomeruli to 1.58 kPa. These results show that the E of glomeruli is between 2 and 4 kPa. E of the GBM, 2.4 kPa, is consistent with this value, and is supported by the behavior of podocytes and mesangial cells grown on variable stiffness matrices. The podocyte cytoskeleton contributes the major component to the overall E of glomeruli, and a normal E requires ATP synthesis. The reduction in glomerular E following ischemia and in other diseases indicates that reduced glomerular E is a common feature of many forms of glomerular injury and indicative of an abnormal podocyte cytoskeleton.

BACKGROUND: The risk of a subsequent stroke following a minor stroke is high. However, there are no effective rating scales to predict recurrent stroke following a minor one. Therefore, we assessed the risk factors associated with recurrent ischemic stroke or transient ischemic attack (TIA) within one year of minor stroke onset in order to identify possible risk factors. METHODS: Eight hundred and sixty-three non-cardioembolic ischemic stroke patients in the Chinese IntraCranial AtheroSclerosis Study that presented with minor stroke, defined as an admission National Institutes of Health stroke scale (NIHSS) score of ≤3, were consecutively enrolled in our study. Clinical information and imaging features upon admission, and any recurrent ischemic stroke or TIA within one year was recorded. Cox regression was used to identify risk factors associated with recurrent ischemic stroke or TIA within the year following stroke onset. RESULTS: A total of 50 patients (6.1%) experienced recurrent ischemic stroke or TIA within one year of minor stroke onset. Multivariate Cox regression model identified lower admission NIHSS score (HR, 1.75; 95% CI, 1.32 to 2.33; P

The adzuki bean (Vigna angularis (Ohwi) Ohwi and Ohashi) is an important grain legume of Asia. It is cultivated mainly in China, Japan and Korea. Despite its importance, few genomic resources are available for molecular genetic research of adzuki bean. In this study, we developed EST-SSR markers for the adzuki bean through next-generation sequencing. More than 112 million high-quality cDNA sequence reads were obtained from adzuki bean using Illumina paired-end sequencing technology, and the sequences were de novo assembled into 65,950 unigenes. The average length of the unigenes was 1,213 bp. Among the unigenes, 14,547 sequences contained a unique simple sequence repeat (SSR) and 3,350 sequences contained more than one SSR. A total of 7,947 EST-SSRs were identified as potential molecular markers, with mono-nucleotide A/T repeats (99.0%) as the most abundant motif class, followed by AG/CT (68.4%), AAG/CTT (30.0%), AAAG/CTTT (26.2%), AAAAG/CTTTT (16.1%), and AACGGG/CCCGTT (6.0%). A total of 500 SSR markers were randomly selected for validation, of which 296 markers produced reproducible amplicons with 38 polymorphic markers among the 32 adzuki bean genotypes selected from diverse geographical locations across China. The large number of SSR-containing sequences and EST-SSR markers will be valuable for genetic analysis of the adzuki bean and related Vigna species.

Patients with symptomatic intracranial atherosclerosis (ICAS) of ≥ 70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset.Patients with a symptomatic ICAS lesion of 70-99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year.Overall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (-2.46-0.79), 4.5 (2.2-20.6), and 7.4 (5.2-12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004-1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002-1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594-0.903; P = 0.014) and 0.776 (95% CI, 0.594-0.903; P = 0.002) in receiver operating characteristic analysis.Hemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70-99% luminal stenosis.

BACKGROUND: Previous economic studies conducted in developed countries showed intravenous tissue-type plasminogen activator (tPA) is cost-effective for acute ischemic stroke. The present study aimed to determine the cost-effectiveness of tPA treatment in China, the largest developing country. METHODS: A combination of decision tree and Markov model was developed to determine the cost-effectiveness of tPA treatment versus non-tPA treatment within 4.5 hours after stroke onset. Outcomes and costs data were derived from the database of Thrombolysis Implementation and Monitor of acute ischemic Stroke in China (TIMS-China) study. Efficacy data were derived from a pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Costs and quality-adjusted life-years (QALYs) were compared in both short term (2 years) and long term (30 years). One-way and probabilistic sensitivity analyses were performed to test the robustness of the results. RESULTS: Comparing to non-tPA treatment, tPA treatment within 4.5 hours led to a short-term gain of 0.101 QALYs at an additional cost of CNY 9,520 (US$ 1,460), yielding an incremental cost-effectiveness ratio (ICER) of CNY 94,300 (US$ 14,500) per QALY gained in 2 years; and to a long-term gain of 0.422 QALYs at an additional cost of CNY 6,530 (US$ 1,000), yielding an ICER of CNY 15,500 (US$ 2,380) per QALY gained in 30 years. Probabilistic sensitivity analysis showed that tPA treatment is cost-effective in 98.7% of the simulations at a willingness-to-pay threshold of CNY 105,000 (US$ 16,200) per QALY. CONCLUSIONS: Intravenous tPA treatment within 4.5 hours is highly cost-effective for acute ischemic strokes in China.

Alfalfa (Medicago sativa L.) is one of the most important forage crops used to feed livestock, such as cattle and sheep, and the sulfur amino acid (SAA) content of alfalfa is used as an index of its nutritional value. Aspartate kinase (AK) catalyzes the phosphorylation of aspartate to Asp-phosphate, the first step in the aspartate family biosynthesis pathway, and adenylylsulfate reductase (APR) catalyzes the conversion of activated sulfate to sulfite, providing reduced sulfur for the synthesis of cysteine, methionine, and other essential metabolites and secondary compounds. To reduce the feedback inhibition of other metabolites, we cloned bacterial AK and APR genes, modified AK, and introduced them into alfalfa. Compared to the wild-type alfalfa, the content of cysteine increased by 30% and that of methionine increased substantially by 60%. In addition, a substantial increase in the abundance of essential amino acids (EAAs), such as aspartate and lysine, was found. The results also indicated a close connection between amino acid metabolism and the tricarboxylic acid (TCA) cycle. The total amino acid content and the forage biomass tested showed no significant changes in the transgenic plants. This approach provides a new method for increasing SAAs and allows for the development of new genetically modified crops with enhanced nutritional value.

BACKGROUND AND PURPOSE: Few studies have reported on the risk factors of dilated Virchow-Robin Spaces (dVRS) in large samples of ischemic stroke patients. Little evidence exists regarding the relationship between dVRS and etiologic subtype of ischemic stroke or lacune. We aimed to investigate the risk factors associated with the severity of dVRS in a large sample of ischemic stroke patients. METHODS: We consecutively enrolled 1,090 patients who experienced an ischemic stroke within the past seven days and underwent a 3.0 T MRI scan in the Chinese IntraCranial AtheroSclerosis Study (ICAS). Clinical data and cranial MRI information of patients included age, sex, vascular risk factors, dVRS, leukoaraiosis, lacune, and etiologic subtype of ischemic stroke. Analyses were performed regarding the risk factors associated with the severity of dVRS by univariate analysis and multivariable ordinal logistic regression analysis. RESULTS: Through multivariable ordinal logistic regression analysis, age, the severity of leukoaraiosis, lacune, admission National Institutes of Health Stroke Scale (NIHSS) ≤3, and the severity of dVRS in the white matter (WM) and hippocampus (Hip) were correlated with the severity of dVRS in basal ganglia (BG); male, history of hypertension, admission NIHSS ≤3, and the severity of dVRS in BG and Hip were correlated with the severity of dVRS in WM; female, the severity of leukoaraiosis, admission NIHSS >3, small artery occlusion subtype of ischemic stroke, and the severity of dVRS in BG and WM were correlated with the severity of dVRS in Hip. CONCLUSION: dVRS is an indicator of cerebral small vessel diseases such as leukoaraiosis and lacune. However, the risk factors of dVRS differ in various brain regions.

BACKGROUND: Statins reportedly improve clinical outcomes for ischemic stroke patients. However, it is unclear whether the contribution of statin treatment varies depending on the severity of stroke. We sought to investigate the relationship between statin use and the outcome of acute first-ever ischemic stroke patients stratified by stroke severity. METHODS: A total of 7,455 acute first-ever ischemic stroke patients without statin treatment before onset were eligible from the China National Stroke Registry. A National Institutes of Health Stroke Scale (NIHSS) score of 0 to 4 was defined as minor stroke, and a NIHSS score of >4 was defined as non-minor stroke. We analyzed the association between statin use during hospitalization and mortality as well as functional outcome (measured by a modified Rankin Scale score of 0-5) at 3 months after onset using multivariable logistic regression models. RESULTS: A total of 3,231 (43.3%) patients received statin treatment during hospitalization. Multivariable analysis showed that statin use during hospitalization decreased mortality of ischemic stroke patients (OR, 0.51; 95%CI, 0.38-0.67), but did not improve poor functional outcomes (OR, 0.95; 95CI%, 0.81-1.11) at 3 months. The interaction between statin use and stroke severity was significant both in dependence and death outcome (P = 0.04 for dependence outcome, P = 0.03 for death outcome). After stratification by stroke severity, statin use during hospitalization decreased the mortality of stroke (OR, 0.44; 95%CI, 0.31-0.62) and poor functional outcome (OR, 0.73; 95%CI, 0.57-0.92) at 3 months in the non-minor stroke group. CONCLUSIONS: Statin use during hospitalization may improve the clinical outcome of acute first-ever ischemic stroke depending on the severity of stroke. Non-minor stroke patients may obtain benefit from statin treatment with improvements in poor functional outcomes and mortality.

BackgroundIntracranial atherosclerotic stenosis (ICAS) is an important cause of ischemic stroke worldwide. The role of high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein cholesterol (LDL-C) in the development of ICAS remains to be elucidated. In the current study, we investigated the relationship of HDL-C level and the risk of developing ICAS in Chinese patients with acute ischemic stroke.MethodsFrom October 2007 to June 2009, a total of 1,984 consecutive ischemic stroke patients were evaluated for the presence of symptomatic ICAS by magnetic resonance angiography (MRA). Patients were classified into two groups: intracranial steno-occlusion (ICAS group, n = 888) and non-intracranial stenosis (NICAS group, n = 1096). Serum lipid profiles were analyzed and compared between the ICAS and NICAS group.ResultsSignificantly more patients in ICAS group had low HDL-C level (51.6%) than in the NICAS group (42.9%, PConclusionsLow HDL-C level is strongly associated with the development of ICAS. There was an inverse relationship between the level of HDL-C and the risk of developing ICAS.

BACKGROUND: The efficacy of antihypertensive (AH) treatment after stroke has been investigated in several randomized clinical trials. However, non-adherence to AH medication is common for stroke patients in "real world" setting. The purpose of this study was to assess the impact of persistence with AH agents on ischemic stroke (IS) outcomes. METHODS AND RESULTS: Using the China National Stroke Registry, we analyzed data from 8409 IS patients with hypertension. Persistence with AH therapy (high persistence ≥75%, low persistence

Berberine, an isoquinoline alkaloid, is an active component of Ranunculaceae and Papaveraceae plant families. Berberine has been found to suppress growth of several tumor cell lines in vitro through the cell-type-dependent mechanism. Expression and activation of epidermal growth factor receptor (EGFR) is increased in colonic precancerous lesions and tumours, thus EGFR is considered a tumour promoter. The aim of this study was to investigate the effects and mechanisms of berberine on regulation of EGFR activity and proliferation in colonic tumor cell lines and in vivo. We reported that berberine significantly inhibited basal level and EGF-stimulated EGFR activation and proliferation in the immorto Min mouse colonic epithelial (IMCE) cells carrying the APC(min) mutation and human colonic carcinoma cell line, HT-29 cells. Berberine acted to inhibit proliferation through inducing G1/S and G2/M cell cycle arrest, which correlated with regulation of the checkpoint protein expression. In this study, we also showed that berberine stimulated ubiquitin ligase Cbl activation and Cbl's interaction with EGFR, and EGFR ubiquitinylation and down-regulation in these two cell lines in the presence or absence of EGF treatment. Knock-down Cbl expression blocked the effects of berberine on down-regulation of EGFR and inhibition of proliferation. Furthermore, berberine suppressed tumor growth in the HT-29 cell xenograft model. Cell proliferation and EGFR expression level was decreased by berberine treatment in this xenograft model and in colon epithelial cells of APC(min/+) mice. Taken together, these data indicate that berberine enhances Cbl activity, resulting in down-regulation of EGFR expression and inhibition of proliferation in colon tumor cells.

Intracranial arterial stenosis (ICAS) is the predominant cause of ischemic stroke and transient ischemic attack in Asia. Change of signal intensities (SI) across an ICAS on magnetic resonance angiography (MRA) may reflect its hemodynamic severity.In-patients with a symptomatic single ICAS detected on 3D time-of-flight MRA were recruited from 2 hospitals. Baseline and 1-year follow-up data were collected. Signal intensity ratio (SIR) [ = (mean post-stenotic SI -mean background SI)/(mean pre-stenotic SI - mean background SI)] was evaluated on baseline MRA to represent change of SIs across an ICAS. Acute infarct volume was measured on baseline diffusion-weighted images (DWI). Relationships between SIR and baseline characteristics as well as 1y outcomes were evaluated.Thirty-six subjects (86.1% males, mean age 55.0) were recruited. Overall, mean SIR was 0.84±0.23. Mean SIRs were not significantly different between the 23 (63.9%) anatomically severe stenoses and the 13 (36.1%) anatomically moderate stenoses (0.80±0.23 versus 0.92±0.21, p = 0.126). SIR was significantly, linearly and negatively correlated to acute infarct volume on DWI (Spearman correlation coefficient -0.471, p = 0.011). Two patients (5.6%) had recurrent ischemic strokes at 1y, not related to SIR values.Change of signal intensities across an ICAS on MRA may reflect its hemodynamic and functional severity. Future studies are warranted to further verify the relationships between this index and prognosis of patients with symptomatic ICAS.

OBJECTIVE: Hyperglycemia is related to stroke. Glycated hemoglobin (HbA1c) can reflect pre-stroke glycaemia status. However, the information on the direct association between HbA1c and recurrence after non-cardioembolic acute ischemic strokes is rare and there is no consistent conclusion. METHODS: The ACROSS-China database comprised of 2186 consecutive first-ever acute ischemic stroke patients with baseline HbA1c values. After excluding patients who died from non-stroke recurrence and patients lost to follow up, 1817 and 1540 were eligible for 3-month and 1-year analyses, respectively. Multivariate Cox regression was performed to evaluate the associations between HbA1c and 3-month and 1-year stroke recurrence. RESULTS: The HbA1c values at admission were divided into 4 levels by quartiles: Q1 (

OBJECTIVES: To analyze the effect of metabolic syndrome (MetS) on prognosis of ischemic stroke secondary to intracranial stenosis in Chinese patients. METHODS: A prospective cohort of 701 patients with ischemic stroke, caused by intracranial stenosis, were followed at 3-month intervals for 1 year to monitor development of recurrent stroke or death. Imaging was performed using magnetic resonance angiography. MetS was defined using International Diabetes Federation (IDF) criteria. RESULTS: MetS was identified in 26.0% of the cohort of stroke patients. Patients with MetS were more likely to be female, nonsmokers, and more likely to have a prior history of diabetes mellitus, high blood glucose and a family history of stroke than patients without MetS. During 1-year follow-up, patients with MetS had a non-significantly higher rate of stroke recurrence (7.1%) than patients without MetS (3.9%; P = 0.07). There was no difference in mortality (3.3% versus 3.5%, respectively). Multivariate Cox proportional hazards analysis (adjusting for gender, BMI, smoking, diabetes, and LDL-C) identified an association between that 1-year stroke recurrence and the presence of MetS (hazard ratio 2.30; 95% CI: 1.01-5.22) and large waist circumference (hazard ratio: 2.39; 95% CI: 1.05-5.42). However, multivariable analysis adjusting for the individual components of MetS found no significant associations between MetS and stroke recurrence. There were no associations between these parameters and mortality. CONCLUSIONS: Chinese patients with symptomatic intracranial atherosclerosis who have MetS, are at higher risk of recurrent stroke than those without MetS. However, MetS was not predictive of stroke recurrence beyond its individual components and one-year mortality.

Berberine, an isoquinoline alkaloid derived from plants, is a traditional medicine for treating bacterial diarrhea and intestinal parasite infections. Although berberine has recently been shown to suppress growth of several tumor cell lines, information regarding the effect of berberine on colon tumor growth is limited. Here, we investigated the mechanisms underlying the effects of berberine on regulating the fate of colon tumor cells, specifically the mouse immorto-Min colonic epithelial (IMCE) cells carrying the Apc(min) mutation, and of normal colon epithelial cells, namely young adult mouse colonic epithelium (YAMC) cells. Berberine decreased colon tumor colony formation in agar, and induced cell death and LDH release in a time- and concentration-dependent manner in IMCE cells. In contrast, YAMC cells were not sensitive to berberine-induced cell death. Berberine did not stimulate caspase activation, and PARP cleavage and berberine-induced cell death were not affected by a caspase inhibitor in IMCE cells. Rather, berberine stimulated a caspase-independent cell death mediator, apoptosis-inducing factor (AIF) release from mitochondria and nuclear translocation in a ROS production-dependent manner. Amelioration of berberine-stimulated ROS production or suppression of AIF expression blocked berberine-induced cell death and LDH release in IMCE cells. Furthermore, two targets of ROS production in cells, cathepsin B release from lysosomes and PARP activation were induced by berberine. Blockage of either of these pathways decreased berberine-induced AIF activation and cell death in IMCE cells. Thus, berberine-stimulated ROS production leads to cathepsin B release and PARP activation-dependent AIF activation, resulting in caspase-independent cell death in colon tumor cells. Notably, normal colon epithelial cells are less susceptible to berberine-induced cell death, which suggests the specific inhibitory effects of berberine on colon tumor cell growth.

Nanopores have become an important tool for molecule detection at single molecular level. With the development of fabrication technology, synthesized solid-state membranes are promising candidate substrates in respect of their exceptional robustness and controllable size and shape. Here, a 30-60 (tip-base) nm conical nanopore fabricated in 100 nm thick silicon nitride (Si(3)N(4)) membrane by focused ion beam (FIB) has been employed for the analysis of λ-DNA translocations at different voltage biases from 200 to 450 mV. The distributions of translocation time and current blockage, as well as the events frequencies as a function of voltage are investigated. Similar to previously published work, the presence and configurations of λ-DNA molecules are characterized, also, we find that greater applied voltages markedly increase the events rate, and stretch the coiled λ-DNA molecules into linear form. However, compared to 6-30 nm ultrathin solid-state nanopores, a threshold voltage of 181 mV is found to be necessary to drive DNA molecules through the nanopore due to conical shape and length of the pore. The speed is slowed down ∼5 times, while the capture radius is ∼2 fold larger. The results show that the large nanopore in thick membrane with an improved stability and throughput also has the ability to detect the molecules at a single molecular level, as well as slows down the velocity of molecules passing through the pore. This work will provide more motivations for the development of nanopores as a Multi-functional sensor for a wide range of biopolymers and nano materials.

OBJECTIVE: Metabolic syndrome has emerged as a novel risk factor in cardiovascular disease due to its potential for predicting stroke in population-based studies. We investigated the relationship of metabolic syndrome with stroke recurrence. METHODS: This was a retrospective analysis of Chinese patients enrolled in the prospective Abnormal gluCose Regulation in patients with acute strOke acroSS China (ACROSS-China) study after their first ischemic stroke. Metabolic syndrome was defined using the International Diabetes Federation (IDF) criteria. Vascular risk factors were assessed. Outcome was defined as recurrence of stroke within one year after the index ischemic stroke. Cox proportional hazards regression was performed to identify potential predictors of stroke recurrence. RESULTS: The prevalence of metabolic syndrome among 2639 ischemic stroke patients was 51.35%. During the one-year follow-up, 195 strokes (7.4%) recurred. The multivariate hazard ratio (95% CI) of stroke recurrence was 1.94 (1.39-2.73) for metabolic syndrome. After adjustment for components, metabolic syndrome lost its association with stroke recurrence; in this model, high fasting plasma glucose (IDF definition) was a predictor for stroke recurrence. CONCLUSION: Metabolic syndrome may not be predictive for stroke recurrence beyond its component individual factors for Chinese ischemic stroke patients.