Citrus peel extract protects against diesel exhaust particle-induced chronic obstructive pulmonary disease-like lung lesions and oxidative stress.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and characterized by emphysema, small airway remodeling and mucus hypersecretion. Citrus peels have been widely used as food spices and in traditional Chinese medicine for chronic lung disease. Given that citrus peels are known for containing antioxidants and anti-inflammatory compounds, we hypothesize that citrus peel intake can suppress oxidative stress and inflammatory response to air pollution exposure, thereby alleviating COPD-like pathologies. This study aimed to investigate the efficacy of citrus peel extract, namely Guang Chenpi (GC), in preventing the development of COPD induced by diesel exhaust particles (DEPs) and its potential mechanism. DEP-induced COPD-like lung pathologies, inflammatory responses and oxidative stress with or without GC treatment were examined in vivo and in vitro. Our in vivo study showed that GC was effective in decreasing inflammatory cell counts and inflammatory mediator (IL-17A and TNF-α) concentrations in bronchoalveolar lavage fluid (BALF). Pretreatment with GC extract also significantly decreased oxidative stress in the serum and lung tissue of DEP-induced COPD rats. Furthermore, GC pretreatment effectively reduced goblet cell hyperplasia (PAS positive cells) and fibrosis of the small airways, decreased macrophage infiltration as well as carbon loading in the peripheral lungs, and facilitated the resolution of emphysema and small airway remodeling in DEP-induced COPD rats. An in vitro free radical scavenging assay revealed robust antioxidant potential of GC in scavenging DPPH free radicals. Moreover, GC demonstrated potent capacities in reducing ROS production and enhancing SOD activity in BEAS-2B cells stimulated by DEPs. GC treatment significantly attenuated the increased level of IL-8 and MUC5AC from DEP-treated BEAS-2B cells. Mechanistically, GC treatment upregulated the protein level of Nrf-2 and could function via MAPK/NF-κB signaling pathways by suppressing the phosphorylation of p38, JNK and p65. Citrus peel extract is effective in decreasing oxidative stress and inflammatory responses of the peripheral lungs to DEP exposure. These protective effects further contributed to the resolution of COPD-like pathologies.

Cortical Venous Changes on Susceptibility-Weighted Imaging Predict the Cerebral Collateral Circulation as Confirmed by Digital Subtraction Angiography.

Objective: Asymmetrical cortical vein sign (ACVS) shown on susceptibility-weighted imaging (SWI) can reflect regional hypoperfusion. We investigated if ACVS could predict the cerebral collateral circulation (CC) as assessed by digital subtraction angiography (DSA) in acute ischemic stroke patients with ipsilateral severe stenosis/occlusion of the anterior circulation. Methods: Clinical data and imaging data of 62 acute ischemic stroke patients with ipsilateral severe stenosis or occlusion of the anterior circulation confirmed by DSA were collected retrospectively. Participants underwent magnetic resonance imaging, including an SWI sequence. ACVS was defined as more and/or larger venous signals in the cerebral cortex of one side of SWI than that in the contralateral side. ACVS was measured using the Alberta Stroke Program Early Computed Tomography score based on SWI. The grading of the cerebral CC was judged using DSA. Results: Of the 62 patients, 30 patients (48.4%) had moderate-to-severe ACVS. According to DSA assessment, 19 patients (30.6%) had a good CC (grade 3-4), and 43 (69.4%) patients had a poor-to-moderate CC (grade 0-2). Among the 30 patients with moderate-to-severe ACVS, only three (10%) patients had a good CC, and 27 (90%) patients had a poor-to-moderate CC; among the 32 patients with none or mild ACVS, 16 (50%) of them had a good CC, and the other 50% had a moderate-to-severe CC. We constructed two logistic regression models with ACVS grading and none or mild ACVS entered into the models, respectively, together with age and large-artery occlusion. In model 1, no ACVS (compared with severe ACVS; OR = 40.329, 95%CI = 2.817-577.422, P = 0.006), mild ACVS (compared with severe ACVS; OR = 17.186, 1.735-170.224, 0.015) and large-artery occlusion (OR = 45.645, 4.603-452.592, 0.001) correlated with a good CC. In model 2, none or mild ACVS (OR = 36.848, 95%CI = 5.516-246.171, P < 0.001) was significantly associated with a good CC as judged by DSA, adjusted by age and large-artery occlusion. Conclusions: Cortical venous changes in SWI may be a useful indicator for the cerebral CC as confirmed by DSA.

Severity of Lesions Involving the Cortical Cholinergic Pathways May Be Associated With Cognitive Impairment in Subacute Ischemic Stroke.

Purpose: Impairment of cortical cholinergic pathways (CCP) is an important risk factor for chronic vascular cognitive impairment. However, this phenomenon has rarely been studied in post-stroke cognitive impairment (PSCI). We investigated the relationship between PSCI and CCP lesions assessed by structural magnetic resonance imaging (MRI). Patients and methods: We prospectively enrolled 103 patients within 7 days of ischemic stroke onset. CCP was measured by the cholinergic pathways hyperintensities scale (CHIPS), which semiquantitatively grades MR lesions strategically located on the CCP identified in human brains. We also measured other MRI parameters, including the location and volumes of acute infarcts, cerebral microbleeds, medial temporal lobe atrophy, and white matter lesions. Neuropsychological assessments were performed using the 60-min modified vascular dementia battery (VDB) at 3 months after the index stroke, and PSCI was defined according to VDB as well as ADL. Results: Of all 103 patients, 69 men (67.0%) and 34 women (33.0%) with a mean age of 57.22 ± 12.95 years, 55 patients (53.4%) were judged to have PSCI at 3 months, including 43 (41.7%) patients with PSCI-no dementia and 12 (11.7%) patients with poststroke dementia. According to the VBD assessment, the most commonly impaired cognitive domain was visuomotor speed (27.2%) followed by verbal memory (25.2%). Univariate analysis showed that patients with PSCI were older; had higher informant questionnaire on cognitive decline in the elderly (IQCODE) scores; had more frequent previous stroke history and atrial fibrillation; and had higher CHIPS scores, more severe white matter lesions, and medial temporal lobe atrophy. PSCI patients also had higher depression scores at 3 months. In the multivariate regression analysis, age, IQCODE score, CHIPS score, and Hamilton depression rating scale score were independent predictors of PSCI. Ordinal regression analysis for risk factors of poor functional outcomes revealed that IQCODE scores and cognitive function status were related to mRS score at 3 months after stroke. Conclusion: In patients with early subacute ischemic stroke, the severity of lesions involving the CCP may be associated with cognitive impairment at 3 months. Clinical Trial Registration: Chinese Clinical Trial Registry, identifier: ChiCTR1800014982.

Diurnal Blood Pressure and Heart Rate Variability in Hypertensive Patients with Cerebral Small Vessel Disease: A Case-Control Study.

BACKGROUND: Whether autonomic dysfunction contributes to cerebral small vessel disease (CSVD) remains unclear. This study aimed to explore the relationship between CSVD and blood pressure variability (BPV) and heart rate variability (HRV). METHODS: This case-control study recruited 50 patients with CSVD and 50 non-CSVD hypertensive age- and gender-matched controls. All participants completed a 24-h ambulatory electrocardiogram recording and ambulatory BP monitoring (ABPM). Differences in HRV and BPV between the two groups were examined. BPV indices assessed by ABPM included mean systolic BP (SBP), mean diastolic BP (DBP), coefficient of variation and weighted standard deviation of SBP and DBP. RESULTS: CSVD patients had significant higher 24-h mean systolic BP (SBP), 24-h mean diastolic BP (DBP), daytime mean SBP, nocturnal mean SBP, and nocturnal mean DBP (P < .05 for all). CSVD patients had a significant lower nocturnal SBP fall rate compared with controls (median: 1.0 versus 6.2, respectively; P < .001) and were more likely to be non-dippers and reverse dippers. There were no differences in HRV variables between the two groups. Five logistic models were built to explore the correlations between BPV indices and CSVD. BPV indices were separately entered into the logistic regression models, together with hyperlipidemia, ischemic stroke history, current use of anti-hypertensive agents, and serum blood urea nitrogen. In models 1-3, 24-h mean SBP and nocturnal mean SBP and DBP were significantly correlated with CSVD (r2 = 0.308-0.340). In model 4, the nocturnal SBP fall rate was negatively correlated with CSVD (odds ratio [OR] = 0.871, 95% confidence interval [CI] = 0.804-0.943; P = .001), with r2 = 0.415 fitting the model. In model 5, the pattern of SBP dipping was significantly associated with CSVD, with non-dipper (OR = 8.389, 95%CI = 1.489-47.254; P = .016) and reverse dipper (OR = 27.008, 95%CI = 3.709-196.660; P = .001) having the highest risks of CSVD (r2 = 0.413). CONCLUSIONS: Lower nocturnal SBP fall rate is associated with CSVD. Non-dipper and reverse dipper hypertensive patients have a higher risk of CSVD.

Global cortical atrophy may be associated with fatigue in patients with parkinson's disease.

PURPOSE: Fatigue has been recognized as a common non-motor problem in patients with Parkinson's disease (PD). The determination of the clinical correlates of fatigue in PD patients is necessary. The purpose of this study was to explore the risk factors related to the severity of fatigue in PD. PATIENTS AND METHODS: In this study, 141 patients with PD were recruited. All patients were evaluated comprehensively, including motor function, fatigue severity scale (FSS), cognition and psychiatric status. Brain magnetic resonance imaging (MRI) examinations were performed to assess the severity of white matter hyperintensities, and the presence of silent lacunes, medial temporal lobe atrophy (MTLA), and global cortical atrophy (GCA). The crude associations of variables with FSS were examined using Pearson (nor-mally distributed) or Spearman correlation (categorical or non-normal distributed) analyses. Multiple linear regression analysis was performed to find the correlates of fatigue severity in PD patients. RESULTS: In the whole sample, with FSS as the dependent variable in a linear regression model, Hamilton Depression Rating Scale (HAM-D), GCA, female sex were significant correlates of FSS, accounting for 24% of the variance of it. When subjects with depression (HAM-D ≥ 35) were excluded, HAM-D, GCA, female sex remained significant correlates of FSS, accounting for 22% of the variance of FSS. There is no correlation between white matter hyperintensities and FSS. CONCLUSION: GCA may be an important correlate of the fatigue severity commonly observed in PD patients.

Asymmetrical cortical vein sign predicts early neurological deterioration in acute ischemic stroke patients with severe intracranial arterial stenosis or occlusion.

BACKGROUND: Susceptibility weighted imaging (SWI) provides an approximate assessment of tissue perfusion and shows prominent hypointense cortical veins in the ischemic territory because of the increased concentration of deoxyhemoglobin. We aimed to evaluate whether asymmetrical prominent cortical vein sign (APCVS) on SWI can predict early neurological deterioration (END) in acute ischemic stroke patients with severe intracranial arterial stenosis or occlusion (SIASO). METHODS: One hundred and nine acute ischemic stroke patients with SIASO who underwent SWI were retrospectively recruited. END was defined as an increase in the National Institutes of Health Stroke Scale score ≧2 points despite standard treatment in the first 72 h after admission. The APCVS was defined as more and/or large vessels with greater signal loss than those in the opposite hemisphere on SWI. RESULTS: Thirty out of the 109 (27.5%) patients developed END. Sixty (55.0%) patients presented with APCVS on SWI. APCVS occurred in 24 (80%) patients with END, whereas it only occurred in 36 (45.6%) patients without END (P = 0.001). Patients with APCVS were more likely to have END (40.0%, vs. 12.2%, P = 0.001) than those without END. Multivariate logistic regression indicated that APCVS (OR = 4.349, 95% C.I. = 1.580-11.970, P = 0.004) was a significant predictor of END in acute ischemic stroke patients with SIASO, adjusted for previous stroke history and acute infarct volume. CONCLUSIONS: In acute ischemic stroke patients with SIASO, the APCVS might be a useful neuroimaging marker for predicting END, which suggests the importance of evaluation of perfusion status.

Accumulated Clinical Experiences from Successful Treatment of 1377 Severe and Critically Ill COVID-19 Cases.

In late December 2019, COVID-19 was firstly recognized in Wuhan, China and spread rapidly to all of the provinces of China. The West Campus of Wuhan Union Hospital, the designated hospital to admit and treat the severe and critically ill COVID-19 cases, has treated a large number of such patients with great success and obtained lots of valuable experiences based on the Chinese guideline (V7.0). To standardize and share the treatment procedures of severe and critically ill cases, Wuhan Union Hospital has established a working group and formulated an operational recommendation, including the monitoring, early warning indicators, and several treatment principles for severe and critically ill cases. The treatment experiences may provide some constructive suggestions for treating the severe and critically ill COVID-19 cases all over the world.

Asymmetrical cortical vessel sign predicts prognosis after acute ischemic stroke.

INTRODUCTION: To assess whether the asymmetrical cortical vessel sign (ACVS) on susceptibility-weighted imaging (SWI) could predict 90-day poor outcomes in anterior circulation acute ischemic stroke (AIS) patients treated with recombinant tissue plasminogen activator (r-tPA). METHODS: Clinical data of consecutive patients with anterior circulation AIS treated with r-tPA were retrospectively analyzed. Clinical variables included age, sex, vascular risk factors, NIHSS score, onset to treatment time, and initial hematologic and neuroimaging findings. Follow-up was performed 90 days after onset. Poor outcome was defined as a modified Rankin scale (mRS) ≥3 at 90 days. RESULTS: A total of 145 patients were included, 35 (24.1%) patients presented with ACVS (≥Grade 1) on SWI. Fifty-three (36.6%) patients had a poor outcome at 90 days. ACVS (≥Grade 1) occurred in 21 (39.6%) patients with poor outcome compared with 14 (15.2%) patients with favorable outcome (p = .001). Univariate analysis indicated that age, NIHSS score on admission, previous stroke, hemorrhagic transformation, severe intracranial large artery stenosis or occlusion (SILASO), and ACVS were associated with 90-day poor outcome (p < .05). Since SILASO and ACVS were highly correlated and ACVS had different grades, we used three logistic regression models. Results from the three models showed that ACVS was associated with 90-day poor outcome. CONCLUSIONS: In r-tPA-treated patients with anterior circulation AIS, ACVS might be a helpful neuroimaging predictor for poor outcome at 90 days.

Clinical characteristics and magnetic resonance imaging findings in nine patients with nonalcoholic Wernicke's encephalopathy: a retrospective study.

PURPOSE: Wernicke's encephalopathy (WE) is a severe neurological disorder caused by thiamine deficiency. The most common cause of WE is alcoholism. However, there is a significant paucity of information in the existing literature relating to nonalcoholic WE. In this study, we investigated the clinical characteristics and neuroimaging findings of nine patients with nonalcoholic WE. PATIENTS AND METHODS: We retrospectively collated clinical data from nine patients who had been diagnosed with WE in accordance with established criteria including age, gender, risk factors and clinical manifestations. We also collated initial hematological and neuroimaging findings. RESULTS: The mean age of the nine patients was 54.0±17.1 years; four of these patients (44.4%) were male. All nine patients had a history of fasting (range, 5-47 days) prior to WE. Four of the nine patients (44.4%) exhibited the classical triad, and eight (88.9%) showed alterations in mental status. Magnetic resonance imaging (MRI) scans showed that all nine patients had symmetric lesions of the medial thalamus. MRI also revealed other WE-related lesions in mammillary bodies (22.2%), the periaqueductal region (55.6%), the tectal plate of the midbrain (77.8%), cranial nerve nuclei (77.8%) and in the symmetric subcortical white matter (11.1%). CONCLUSION: Our analysis showed that fasting is a common cause of WE in nonalcoholic patients and that MRI is a useful tool for the diagnosis of WE. The most common MRI findings were symmetrical lesions of the medial thalamus lesions, followed by the tectal plate of the midbrain and cranial nerve nuclei.

Anxiety in Patients With Acute Ischemic Stroke: Risk Factors and Effects on Functional Status.

Background: Anxiety is prevalent after a stroke. The pathophysiological mechanisms underlying the development of poststroke anxiety (PSA) remain unclear. The aim of this study was to investigate the clinical and neuroimaging risk factors for development of PSA and examine the effects of PSA on activities of daily living (ADL) and quality of life (QOL) in Chinese patients with ischemic stroke. Methods: Two hundred nineteen patients with acute ischemic stroke were recruited to the study. A series of comprehensive assessments, including Hamilton Anxiety Rating Scale (HARS), Hamilton Depression Rating Scale (HDRS), Lawton ADL Scale, and the Stroke-Specific Quality of Life (SSQOL) Scale, were conducted in the acute stage and 3 months after stroke. Magnetic resonance imaging assessment focused on evaluation of infarctions, white matter lesions, and brain atrophy. Results: In the acute stage and 3 months after stroke, 34 (16%) and 33 (15%) patients had PSA, respectively. Multiple logistic regression analysis indicated that HDRS (OR = 1.269, 95% CI = 1.182-1.364, P < 0.001) and acute infarcts in cerebral hemispheric white matter (CHWM; OR = 2.902, 95% CI = 1.052-8.007, P = 0.040) were significant correlates of PSA in the acute stage of stroke. Three months after stroke, these correlates remained significant predictors, along with male sex. Multiple linear regressions showed that age, NIHSS, HARS, and HDRS in the acute stage were significant predictors for both ADL and SSQOL at 3 months after stroke. Conclusion: Depressive symptoms are the major correlates of PSA while more severe PSA is associated with poorer ADL and health-related QOL. Acute lesions involving CHWM may correlate with PSA in ischemic stroke patients with mild-to-moderate neurologic deficits, supporting a lesion-location hypothesis in PSA.

Reliability and Validity of Simplified Chinese STOP-BANG Questionnaire in Diagnosing and Screening Obstructive Sleep Apnea Hypopnea Syndrome.

The main purpose of this study was to assess the reliability and validity of the simplified Chinese STOP-BANG Questionnaire (SBQ) as a diagnosing and screening tool for obstructive sleep apnea hypopnea syndrome (OSAHS). Two hundred and ten patients with suspected OSAHS were recruited in this study. The simplified Chinese SBQ was completed twice before and after polysomnography (PSG) monitoring. SPSS 20.0 was used to analyze the test-retest reliability, discriminant validity, comparative validity and predictive validity of the SBQ. Fourteen patients were excluded on account of fragmentary data, and valid 196 were divided into four groups: non-OSAHS group (n=28, 14.29%), mild OSAHS group (n=28, 14.29%), moderate OSAHS group (n=31, 15.81%) and severe OSAHS group (n=109, 55.61%). The test-retest coefficient for the first four items was 0.810, 0.679, 0.775, 0.963 respectively and the total score of the STOP questionnaire was 0.854. The analysis of discriminant validity revealed that there were significant differences among four groups in the total score of the SBQ and scores of item 1, 3, 7 and 8, which were also validated between patients with normal blood oxygen saturation and different degrees of hypoxemia. The SBQ evaluation showed low consistency with diagnostic gold standard PSG (κ=0.303, P<0.05). When taking apnea hypopnea index (AHI) ≥5/h, ≥15/h and ≥30/h as cut-offs to evaluate the SBQ predictive value, the areas under ROC curve were 0.77, 0.81 and 0.78, the sensitivity was 90.48%, 93.57% and 93.33%, and corresponding negative predictive values were 40.74%, 66.67% and 85.19%, respectively. It was suggested that the simplified Chinese version of SBQ had good reliability, and could distinguish the severity of OSAHS. Despite its limited diagnostic accuracy, the SBQ can be considered as an ideal tool for screening OSAHS with superior predictive validity.

Microbleeds in fronto-subcortical circuits are predictive of dementia conversion in patients with vascular cognitive impairment but no dementia.

Cerebral small vessel disease (CSVD) is a common etiology of vascular cognitive impairment with no dementia (V-CIND). Studies have revealed that cerebral microbleeds (CMBs), a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients (29.3%) had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits (odds ratio = 4.4; 95% confidence interval: 1.602-12.081, P = 0.004) and 5 or more CMBs overall (odds ratio = 17.6, 95% confidence interval: 3.23-95.84, P = 0.001) had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs. This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800017077). Protocol version: 1.0.

Intracranial Atherosclerosis and Poststroke Depression in Chinese Patients with Ischemic Stroke.

BACKGROUND: Intracranial atherosclerosis (ICAS) is a common etiology of ischemic stroke in Chinese patients, probably leading to regional hypoperfusion in the brain. The purpose of this prospective study was to investigate the association between ICAS and poststroke depression in Chinese patients with ischemic stroke. METHODS: During the study period, a total of 569 patients aged between 40 and 80 years with acute ischemic stroke were consecutively admitted and screened. Patients with a National Institutes of Health Stroke Scale (NIHSS) total score of 15 or higher, with severe cognitive impairment, or with a history of depression before stroke were excluded. Two hundred seven patients with ischemic stroke were consecutively recruited in the study. Depressive symptoms were assessed in the acute stage and 3 months after stroke. Poststroke depression was defined as a score of 8 or higher in the 24-item Hamilton Depression Rating Scale. The evaluation of the magnetic resonance imaging scans focused on infarctions, white matter lesions, brain atrophy, and ICAS. RESULTS: In the acute stage of stroke, logistic regression revealed that female sex, NIHSS score at admission, prestroke insomnia, and ICAS were significant predictors of poststroke depression. At 3 months after stroke, prestroke insomnia, the Mini-Mental State Examination score and ICAS were significant predictors of poststroke depression. CONCLUSIONS: ICAS may be a significant independent predictor of poststroke depression in Chinese patients with ischemic stroke.

Neuroimaging indicators of the performance of instrumental activities of daily living in Alzheimer's disease combined with cerebrovascular disease.

OBJECTIVES: The aim of the present study was to explore the magnetic resonance imaging correlates of the performance of instrumental activities of daily living (IADL) in patients with Alzheimer's disease combined with cerebrovascular disease. METHODS: A total of 66 patients with Alzheimer's disease combined with cerebrovascular disease formed the study sample. Two regression models were constructed to find correlates of IADL. Model 1 only included clinical variables and model 2 included both clinical and magnetic resonance imaging variables. RESULTS: In model 1, with IADL as the dependent variable, the Mini-Mental State Examination (MMSE) score, Physical Self-Maintenance Scale score at baseline and age were significant correlates accounting for 40.1% of the variance of IADL at baseline. MMSE score and age were also significant correlates of IADL at 6 months, accounting for 38.1% of the variance of it. In model 2, severity of white matter lesions, MMSE and Physical Self-Maintenance Scale scores at baseline significantly correlated with IADL at baseline, accounting for 52.1% of the variance of the dependent variables; severity of white matter lesions and MMSE significantly correlated with IADL at 6 months, accounting for 41.5% of the variance of the dependent variables. CONCLUSION: In patients with Alzheimer's disease combined with cerebrovascular disease, subcortical ischemic lesions might be significant contributor to the functional status.

Poststroke fatigue: risk factors and its effect on functional status and health-related quality of life.

BACKGROUND: Fatigue is a common problem in ischemic stroke survivors. The mechanisms of poststroke fatigue are uncertain yet. The effects of it on functional status have rarely been studied. AIMS: The aim of this study was to investigate the risk factors of poststroke fatigue and its effect on activities of daily living and health-related quality of life in Chinese patients with ischemic stroke. METHODS: Two hundred and eighteen patients with ischemic stroke formed the study sample. A comprehensive assessment, including the Fatigue Severity Scale, Hamilton Depression Rating Scale, Lawton activities of daily living scale, and the stroke-specific quality of life scale, was conducted three-months after stroke. Magnetic resonance imaging scans focused on the evaluation of infarctions, white matter lesions, and brain atrophy. RESULTS: In the whole sample, with Fatigue Severity Scale as the dependent variable in a linear regression model, Hamilton Depression Rating Scale, prestroke fatigue, and the National Institutes of Health Stroke Scale score at admission were significant correlates of Fatigue Severity Scale, accounting for 36% of the variance of it. When subjects with depression (Hamilton Depression Rating Scale ≥ 20 or current usage of antidepressants) were excluded, only Hamilton Depression Rating Scale and prestroke fatigue remained significant correlates of Fatigue Severity Scale, accounting for 33% of the variance of Fatigue Severity Scale. No magnetic resonance imaging variables correlated with Fatigue Severity Scale. In bivariate correlation analyses, Fatigue Severity Scale was significantly correlated with both activities of daily living and stroke-specific quality of life. In linear regression models, Fatigue Severity Scale independently contributed to activities of daily living accounting for 27% of the variance. Fatigue Severity Scale was also a significant contributor to stroke-specific quality of life accounting for 39% of the variance. CONCLUSION: Depressive symptoms and prestroke fatigue are major correlates of poststroke fatigue while more severe poststroke fatigue is associated with poorer activities of daily living and health-related quality of life.

Inordinate glucose variation poststroke is associated with poor neurological improvement in patients without history of diabetes.

INTRODUCTION: Glucose variation is an important risk factor for the complications of diabetes mellitus. The plasma glucose level poststroke is in continuous fluctuation. However, whether the variation influences neurological improvement remains unknown. AIMS: This observational study aimed to investigate the association of glucose variation with neurological improvement poststroke. METHODS: We consecutively enrolled 216 ischemic stroke patients with no history of diabetes mellitus within 72 h of onset, with instant blood glucose <11.1 mmol/L at admission. The glucometabolic status was evaluated by an oral glucose tolerance test 1 day after admission and 14 days after stroke, respectively. The severity of neurological deficit was assessed with the National Institute of Health Stroke Scale (NIHSS). RESULTS: Fourteen days after stroke, 31% patients were found to have impaired glucose tolerance and 30.6% were newly diagnosed diabetes mellitus by oral glucose tolerance test. A higher level of instant blood glucose at admission or fasting plasma glucose (FPG) at 1 day correlated with a less neurological improvement. The number of patients with no <20% decrease in NIHSS was significantly decreased in patient group with higher than 30% variation of either FPG or 2-h postprandial glucose. Similar correlation between glucose variation and neurological improvement was also found in 117 patients with 2-h postprandial glucose ≥7.8 mmol/L at 1 day. CONCLUSIONS: Inordinate glucose variation correlated with less neurological improvement poststroke, giving the evidence that the fluctuation of glucose levels in stroke patients should be taken into consideration during glucose modulation.

Atrophy of the left dorsolateral prefrontal cortex is associated with poor performance in verbal fluency in elderly poststroke women.

This study aimed to investigate the association between atrophy in the prefrontal cortex with executive function and verbal fluency in elderly male and female patients poststroke. Thirty elderly female patients with non-aphasic ischemic stroke aged ≥ 60 years and 30 age-matched non-aphasic male patients with ischemic stroke were recruited. Automatic magnetic resonance imaging segmentation was used to assess the volume of the whole prefrontal cortex, along with its subdivisions: anterior cingulate cortex, orbitofrontal cortex and dorsolateral prefrontal cortex. The Semantic Verbal Fluency Test was administered at 3 and 15 months poststroke. At 3 months poststroke, left dorsolateral prefrontal cortex volume was significantly correlated with Verbal Fluency Test score in female patients only (partial coefficient = 0.453, P = 0.045), after controlling for age, education, diabetes, neurological deficit, white matter lesions volume, as well as the location and volume of infarcts. At 15 months poststroke, there remained a significant association between the left dorsolateral prefrontal cortex volume and Verbal Fluency Test (partial coefficient = 0.661, P = 0.001) and between the left prefrontal cortex volume and Verbal Fluency Test (partial coefficient = 0.573, P = 0.004) in female patients after the same adjustments. These findings indicate that atrophy of the left dorsolateral prefrontal cortex contributes to the impairment of verbal fluency in elderly female patients with stroke. Sex differences may be present in the neuropsychological mechanisms of verbal fluency impairment in patients with stroke.

[HSF1 inhibits heat stress-induced apoptosis in Raw264.7 macrophages].

OBJECTIVE: To observe the effect of heat shock factor 1 (HSF1) on heat stress-induced apoptosis in Raw264.7 macrophages. METHODS: Raw264.7 cells transfected with pcDNA3.1 and pcDNA3.1-HSF1 were exposed to heat stress (42.5 degrees C +/- 0.5 degrees C) for 1 h and recovered at 37 degrees C for 6, 9, 12, and 24 h respectively. Flow cytometry (FCM), Hoechst 33258 staining and DNA ladder assays were performed to assess the apoptosis. RESULTS: After heat stress, FCM showed that apoptotic cells were increased significantly and reached the peak at 9 h in Raw 264.7 cells transfected with pcDNA3.1, and were characterized with classical morphologic changes including apoptotic body and nuclear condensation. Agarose gel electrophoresis showed that "DNA ladder" could be observed clearly at 6, 9, and 12 h after the heat stress. But the overexpression of HSF1 could reduce the number of apoptotic cells and inhibit DNA fragmentation. CONCLUSION: HSF1 can inhibit heat stress-induced apoptosis in Raw264.7 macrophages.

[Roles of nuclear factor-kappaB in heat shock pretreatment to abate cardiomyocyte injury induced by hydrogen peroxide].

OBJECTIVE: To investigate the role of nuclear factor-kappaB (NF-kappaB) in heat shock pretreatment to abate cardiomyocyte injury induced by hydrogen peroxide (H(2)O(2)). METHODS: The primary generation of cultured neonatal rat cardiomyocytes were injured by exposure to 1 mmol/L H(2)O(2) for different durations. The total antioxidant in cardiomyocytes was detected. The changes in heat shock protein 70 (HSP70), alphaB-crystallin, inhibitor of NF-kappaB (I-kappaB) were assayed by Western-blotting. The translocation of NF-kappaB and HSP70 from cytoplasm to nucleus was observed by immunohistochemical analysis. RESULTS: (1)Compared with H(2)O(2) (1 mmol/L, 3 h) treated cells, cells subjected to heat shock pretreatment showed significant increase in total antioxidant capability (all P<0.01). (2)Western blot analysis demonstrated that heat shock pretreatment could induce expression of HSP70, alphaB-crystallin and I-kappaB. (3)Heat shock pretreatment inhibited H(2)O(2)-mediated I-kappaB degradation. (4)Immunohistochemical analysis showed that heat shock pretreatment could abate HSP70 and NF-kappaB translocation from cytoplasm to nucleus. CONCLUSION: Heat shock pretreatment could protect cardiomyocytes against H(2)O(2)-induced injury, and its mechanism might involve expression of HSP70, alphaB-crystallin and I-kappaB, which could inhibit H(2)O(2) -mediated NF-kappaB activation.

[HSP70 inhibits smac release from the mitochondria and protects against H2O2-induced apoptosis in C2C12 myogenic cells].

OBJECTIVE: To observe whether HSP70 could protect against H2O2-induced apoptosis in C2C12 myogenic cells by inhibiting Smac release from the mitochondria. METHODS: HSP70 gene and full length Smac gene was transiently transfected in C2C12 myogenic cells by lipofectamine and the protein levels of HSP70 and Smac were analysed by Western blotting. Hoechst 33 258 staining was used to examine cell morphological changes and to calculate percentage of apoptotic nuclei. DNA ladder pattern on agarose gel electrophoresis was used to observe the DNA fragmentation. Activities of caspase-3 and caspase-9 were assayed with Western blotting. The release of Smac from the mitochondria to the cytoplasm was observed by immunofluorescence. RESULTS: H2O2 ( 0.5 mmol/L ) activated caspase-3, caspase-9 8 h after the treatment and specific morphological changes of apoptosis 12 h after the treatment, and overexpression of Smac significantly promoted H2O2-induced activation of caspase-3, caspase-9 and apoptosis in C2C12 myogenic cells. HSP70 overexpression significantly inhibited H2O2-induced and Smac-promoted apoptosis, as shown by no specific DNA ladder pattern in agarose gel electrophoresis, decrease of percentage of apoptotic nuclei, and marked inactivation of caspase-3 and caspase-9. HSP70 could inhibit the release of Smac from the mitochondria to the cytoplasm 2 h after the treatment by H2O2. CONCLUSION: HSP70 inhibits Smac release from the mitochondria and protects against H2O2-induced apoptosis in C2C12 myogenic cells.