Helpful to Live Healthier? Intermittent Hypoxic/Ischemic Training Benefits Vascular Homeostasis and Lipid Metabolism with Activating SIRT1 Pathways in Overweight/Obese Individuals.

INTRODUCTION: The present study aimed to investigate whether and how normobaric intermittent hypoxic training (IHT) or remote ischemic preconditioning (RIPC) plus normoxic training (RNT) has a synergistic protective effect on lipid metabolism and vascular function compared with normoxic training (NT) in overweight or obese adults. METHODS: A total of 37 overweight or obese adults (36.03 ± 10.48 years) were randomly assigned to 3 groups: NT group (exercise intervention in normoxia), IHT group (exercise intervention in normobaric hypoxic chamber), and RNT group (exercise intervention in normoxia + RIPC twice daily). All participants carried out the same 1-h exercise intervention for a total of 4 weeks, 5 days per week. Physical fitness parameters were evaluated at pre- and postexercise intervention. RESULTS: After training, all three groups had a significantly decreased body mass index (p < 0.05). The IHT group had reduced body fat percentage, visceral fat mass (p < 0.05), blood pressure (p < 0.01), left ankle-brachial index (ABI), maximal heart rate (HRmax) (p < 0.05), expression of peroxisome proliferator-activated receptor-γ (PPARγ) (p < 0.01) and increased expression of SIRT1 (p < 0.05), VEGF (p < 0.01). The RNT group had lowered waist-to-hip ratio, visceral fat mass, blood pressure (p < 0.05), and HRmax (p < 0.01). CONCLUSION: IHT could effectively reduce visceral fat mass and improve vascular elasticity in overweight or obese individuals than pure NT with the activation of SIRT1-related pathways. And RNT also produced similar benefits on body composition and vascular function, which were weaker than those of IHT but stronger than NT. Given the convenience and economy of RNT, both intermittent hypoxic and ischemic training have the potential to be successful health promotion strategies for the overweight/obese population.

Effects of acetazolamide combined with remote ischemic preconditioning on risk of acute mountain sickness: a randomized clinical trial.

BACKGROUND: We aimed to determine whether and how the combination of acetazolamide and remote ischemic preconditioning (RIPC) reduced the incidence and severity of acute mountain sickness (AMS). METHODS: This is a prospective, randomized, open-label, blinded endpoint (PROBE) study involving 250 healthy volunteers. Participants were randomized (1:1:1:1:1) to following five groups: Ripc (RIPC twice daily, 6 days), Rapid-Ripc (RIPC four times daily, 3 days), Acetazolamide (twice daily, 2 days), Combined (Acetazolamide plus Rapid-Ripc), and Control group. After interventions, participants entered a normobaric hypoxic chamber (equivalent to 4000 m) and stayed for 6 h. The primary outcomes included the incidence and severity of AMS, and SpO2 after hypoxic exposure. Secondary outcomes included systolic and diastolic blood pressure, and heart rate after hypoxic exposure. The mechanisms of the combined regime were investigated through exploratory outcomes, including analysis of venous blood gas, complete blood count, human cytokine antibody array, ELISA validation for PDGF-AB, and detection of PDGF gene polymorphisms. RESULTS: The combination of acetazolamide and RIPC exhibited powerful efficacy in preventing AMS, reducing the incidence of AMS from 26.0 to 6.0% (Combined vs Control: RR 0.23, 95% CI 0.07-0.70, P = 0.006), without significantly increasing the incidence of adverse reactions. Combined group also showed the lowest AMS score (0.92 ± 1.10). Mechanistically, acetazolamide induced a mild metabolic acidosis (pH 7.30 ~ 7.31; HCO3- 18.1 ~ 20.8 mmol/L) and improved SpO2 (89 ~ 91%) following hypoxic exposure. Additionally, thirty differentially expressed proteins (DEPs) related to immune-inflammatory process were identified after hypoxia, among which PDGF-AB was involved. Further validation of PDGF-AB in all individuals showed that both acetazolamide and RIPC downregulated PDGF-AB before hypoxic exposure, suggesting a possible protective mechanism. Furthermore, genetic analyses demonstrated that individuals carrying the PDGFA rs2070958 C allele, rs9690350 G allele, or rs1800814 G allele did not display a decrease in PDGF-AB levels after interventions, and were associated with a higher risk of AMS. CONCLUSIONS: The combination of acetazolamide and RIPC exerts a powerful anti-hypoxic effect and represents an innovative and promising strategy for rapid ascent to high altitudes. Acetazolamide improves oxygen saturation. RIPC further aids acetazolamide, which synergistically regulates PDGF-AB, potentially involved in the pathogenesis of AMS. TRIAL REGISTRATION: ClinicalTrials.gov NCT05023941.

Intracranial Spotty Calcium Predicts Recurrent Stroke in Patients with Symptomatic Intracranial Atherosclerotic Stenosis : A Prospective Cohort Study.

PURPOSE: Accumulating evidence highlights the association of calcium characteristics and cardiovascular events, but its role in cerebrovascular stenosis has not been well studied. We aimed to investigate the contribution of calcium patterns and density to recurrent ischemic stroke in patients with symptomatic intracranial atherosclerotic stenosis (ICAS). METHODS: In this prospective study, 155 patients with symptomatic ICAS in the anterior circulation were included, and all subjects underwent computed tomography angiography. The median follow-up for all patients was 22 months and recurrent ischemic stroke were recorded. Cox regression analysis was performed to examine whether calcium patterns and density were associated with recurrent ischemic stroke. RESULTS: During the follow-up, 29 patients who experienced recurrent ischemic stroke were older than those without recurrent ischemic stroke (62.93 ± 8.10 years vs. 57.00 ± 12.07 years, p = 0.027). A significantly higher prevalence of intracranial spotty calcium (86.2% vs. 40.5%, p < 0.001) and very low-density intracranial calcium (72.4% vs. 37.3%, p = 0.001) were observed in patients with recurrent ischemic stroke. Multivariable Cox regression analysis showed that intracranial spotty calcium, rather than very low-density intracranial calcium, remained an independent predictor of recurrent ischemic stroke (adjusted hazard ratio 5.35, 95% confidence interval 1.32-21.69, p = 0.019). CONCLUSION: In patients with symptomatic ICAS, intracranial spotty calcium is an independent predictor of recurrent ischemic stroke, which will further facilitate risk stratification and suggest that more aggressive treatment should be considered for these patients.

Association of Posture Instability with Dopamine Drop of Nigrostriatal System and Hypometabolism of Cerebral Cortex in Parkinson's Disease.

BACKGROUND: Posture Instability (PI) is known to be a severe complication in Parkinson's Disease (PD), and its mechanism remains poorly understood. Our study aims to explore the changes of brain network in PI of PD, and further investigate the role of peripheral inflammation on activities of different brain regions in PD with PI. METHODS: 167 individuals were recruited, including 36 PD cases with PI and 131 ones without PI. We carefully assessed the status of motor and cognitive function, measured serum inflammatory factors, and detected the dopaminergic pathways and the metabolism of different brain regions by Positron Emission Tomography (PET). Data analysis was conducted by variance, univariate analysis, chi-square analysis, logistic regression, and partial correlation. RESULTS: No difference was found for age or onset age between the two groups (P>0.05). Female patients were susceptible to posture impairment and had a 2.14-fold risk for PI compared with male patients in PD (P<0.05). Patients with PI had more severe impairment of motor and cognitive function for a longer duration than those without PI (P<0.05). The mean uptake ratios of presynaptic vesicular monoamine transporter (VMAT2), which were detected in the caudate nucleus and putamen, were lower in PI group than those without PI (P<0.05). There were lower activities of the midbrain, caudate nucleus, and anterior medial temporal cortex in PI group than those in the non-PI group (P<0.05). Although serum concentrations of immunoglobulins (IgG, IgM, and IgA) and complements (C3, C4) were higher in the PI group than those in the non-PI group, only serum IgM concentration had a significant difference between the two groups (P<0.05). We further explored significant inverse correlations of IgG, IgM, IgA, and C4 with activities of some cerebral cortex in PI of PD (P<0.05). CONCLUSION: Female patients were susceptible to posture instability and had a 2.14-fold risk for PI of PD. Patients with PI had more severe impairments of motor and cognitive function for a longer duration than those without PI. PI was associated with a dopamine drop of the nigrostriatal system and lower activities of the limbic cortex in PD. Peripheral inflammation may be involved in degeneration of the cerebral cortex in PD combined with PI.

Acute Ischemic Stroke at High Altitudes in China: Early Onset and Severe Manifestations.

The detailed characteristics of strokes at high altitudes in diverse nations have not been extensively studied. We retrospectively enrolled 892 cases of first-ever acute ischemic strokes at altitudes of 20, 2550, and 4200 m in China (697 cases from Penglai, 122 cases from Huzhu, and 73 cases from Yushu). Clinical data and brain images were analyzed. Ischemic strokes at high altitudes were characterized by younger ages (69.14 ± 11.10 vs. 64.44 ± 11.50 vs. 64.45 ± 14.03, p < 0.001) and larger infract volumes (8436.37 ± 29,615.07 mm3 vs. 17,213.16 ± 47,044.74 mm3 vs. 42,459 ± 84,529.83 mm3, p < 0.001). The atherosclerotic factors at high altitude, including diabetes mellitus (28.8% vs. 17.2% vs. 9.6%, p < 0.001), coronary heart disease (14.3% vs. 1.6% vs. 4.1%, p < 0.001), and hyperlipidemia (20.2% vs. 17.2% vs. 8.2%, p = 0.031), were significantly fewer than those in plain areas. Polycythemia and hemoglobin levels (138.22 ± 18.04 g/L vs. 172.87 ± 31.57 g/L vs. 171.81 ± 29.55 g/L, p < 0.001), diastolic pressure (89.98 ± 12.99 mmHg vs. 93.07 ± 17.79 mmHg vs. 95.44 ± 17.86 mmHg, p = 0.016), the percentage of hyperhomocysteinemia (13.6% in Penglai vs. 41.8% in Huzhu, p < 0.001), and the percentage of smoking (33.1% in Penglai vs. 50.0% in Huzhu, p = 0.023) were significantly elevated at high altitudes. We concluded that ischemic stroke occurred earlier and more severely in the Chinese plateau. While the atherosclerotic factors were not prominent, the primary prevention of strokes at high altitudes should emphasize anticoagulation, reducing diastolic pressure, adopting a healthy diet, and smoking cessation.

LncRNA HCG11/miR-26b-5p/QKI5 feedback loop reversed high glucose-induced proliferation and angiogenesis inhibition of HUVECs.

Acute coronary syndrome caused by the rupture of atherosclerotic plaques is one of the primary causes of cerebrovascular and cardiovascular events. Neovascularization within the plaque is closely associated with its stability. Long non-coding RNA (lncRNA) serves a crucial role in regulating vascular endothelial cells (VECs) proliferation and angiogenesis. In this study, we identified lncRNA HCG11, which is highly expressed in patients with vulnerable plaque compared with stable plaque. Then, functional experiments showed that HCG11 reversed high glucose-induced vascular endothelial injury through increased cell proliferation and tube formation. Meanwhile, vascular-related RNA-binding protein QKI5 was greatly activated. Luciferase reporter assays and RNA-binding protein immunoprecipitation (RIP) assays verified interaction between them. Interestingly, HCG11 can also positively regulated by QKI5. Bioinformatics analysis and luciferase reporter assays showed HCG11 can worked as a competing endogenous RNA by sponging miR-26b-5p, and QKI5 was speculated as the target of miR-26b-5p. Taken together, our findings revered that the feedback loop of lncRNA HCG11/miR-26b-5p/QKI-5 played a vital role in the physiological function of HUVECs, and this also provide a potential target for therapeutic strategies of As.

Intensive Lipid-Lowering Therapy Ameliorates Asymptomatic Intracranial Atherosclerosis.

Statins have proven to exert protective effects in patients with symptomatic intracranial atherosclerotic stenosis (SICAS). It is unclear whether intensive lipid-lowering therapy (ILLT) can ameliorate atherosclerosis in asymptomatic ICAS (AICAS). A single-center, prospective cohort study was performed in 71 AICAS patients with lipid-lowering therapy. Vascular stenoses were evaluated with transcranial color-coded sonography (TCCS) before and after statin treatment. With target therapeutic level of low-density lipoprotein cholesterol (LDL-C) ≤ 1.8 mmol/L or ≥ 50% reduction from baseline after the two years of follow-up, patients were divided into intensive statin treatment (IST) group and standard statin treatment (SST) group. A total of 104 stenotic intracranial arteries were detected in 51 patients belonging to the IST group and 47 arteries in 20 patients of the SST group. In the first year, LDL-C levels were significantly decreased in the IST compared with SST groups (1.48 ± 0.26 vs. 2.20 ± 0.58, P=0.000). However, the ratio of regressed ICAS in IST was not significantly higher than that in SST (26.3% vs. 5.9%, P=0.052). Forty-nine branches in 25 patients of the IST group and 16 branches in 7 patients of the SST group were followed up for two years. The LDL-C level was decreased in the IST compared with SST groups (1.55 ± 0.29 vs. 2.36 ± 0.77, P=0.048). The ratio of regressed ICAS in the IST group was significantly higher than that in SST group (34.7% vs. 6.3%, P=0.017). We concluded that the degree of stenosis in AICAS can be ameliorated with intensive lipid-lowering therapy within two years; target LDL-C level can be reached by moderate-intensity statin treatment for Chinese AICAS patients.

Intracranial Vessel Wall Segmentation Using Convolutional Neural Networks.

OBJECTIVE: To develop an automated vessel wall segmentation method using convolutional neural networks to facilitate the quantification on magnetic resonance (MR) vessel wall images of patients with intracranial atherosclerotic disease (ICAD). METHODS: Vessel wall images of 56 subjects were acquired with our recently developed whole-brain three-dimensional (3-D) MR vessel wall imaging (VWI) technique. An intracranial vessel analysis (IVA) framework was presented to extract, straighten, and resample the interested vessel segment into 2-D slices. A U-net-like fully convolutional networks (FCN) method was proposed for automated vessel wall segmentation by hierarchical extraction of low- and high-order convolutional features. RESULTS: The network was trained and validated on 1160 slices and tested on 545 slices. The proposed segmentation method demonstrated satisfactory agreement with manual segmentations with Dice coefficient of 0.89 for the lumen and 0.77 for the vessel wall. The method was further applied to a clinical study of additional 12 symptomatic and 12 asymptomatic patients with >50% ICAD stenosis at the middle cerebral artery (MCA). Normalized wall index at the focal MCA ICAD lesions was found significantly larger in symptomatic patients compared to asymptomatic patients. CONCLUSION: We have presented an automated vessel wall segmentation method based on FCN as well as the IVA framework for 3-D intracranial MR VWI. SIGNIFICANCE: This approach would make large-scale quantitative plaque analysis more realistic and promote the adoption of MR VWI in ICAD management.

Differential Features of Culprit Intracranial Atherosclerotic Lesions: A Whole-Brain Vessel Wall Imaging Study in Patients With Acute Ischemic Stroke.

BACKGROUND: Intracranial atherosclerotic disease tends to affect multiple arterial segments. Using whole-brain vessel wall imaging, we sought to study the differences in plaque features among various types of plaques in patients with a recent unilateral anterior circulation ischemic stroke. METHODS AND RESULTS: Sixty-one patients with unilateral anterior circulation ischemic stroke were referred to undergo whole-brain vessel wall imaging (before and after contrast) within 1 month of symptom onset for intracranial atherosclerotic disease evaluations. Each plaque was classified as a culprit, probably culprit, or nonculprit lesion, according to its likelihood of causing the stroke. The associations between plaque features (thickening pattern, plaque-wall contrast ratio, high signal on T1-weighted images, plaque contrast enhancement ratio, enhancement grade, and enhancement pattern) and culprit lesions were estimated using mixed multivariable logistic regression after adjustment for maximum wall thickness. In 52 patients without motion corruption in whole-brain vessel wall imaging, a total of 178 intracranial plaques in the anterior circulation were identified, including 52 culprit lesions (29.2%), 51 probably culprit lesions (28.7%), and 75 nonculprit lesions (42.1%). High signal on T1-weighted images (adjusted odds ratio, 9.1; 95% confidence interval, 1.9-44.1; P=0.006), grade 2 (enhancement ratio of plaque ≥ enhancement ratio of pituitary) contrast enhancement (adjusted odds ratio, 17.4; 95% confidence interval, 1.8-164.9; P=0.013), and type 2 (≥50% cross-sectional wall involvement) enhancement pattern (adjusted odds ratio, 10.1; 95% confidence interval, 1.3-82.2; P=0.030) were independently associated with culprit lesions. CONCLUSIONS: High signal on T1-weighted images, grade 2 contrast enhancement, and type 2 enhancement pattern are associated with cerebrovascular ischemic events, which may provide valuable insights into risk stratification.

Quantitative assessment of symptomatic intracranial atherosclerosis and lenticulostriate arteries in recent stroke patients using whole-brain high-resolution cardiovascular magnetic resonance imaging.

BACKGROUND: It has been shown that intracranial atherosclerotic stenosis (ICAS) has heterogeneous features in terms of plaque instability and vascular remodeling. Therefore, quantitative information on the changes of intracranial atherosclerosis and lenticulostriate arteries (LSAs) may potentially improve understanding of the pathophysiological mechanisms underlying stroke and may guide the treatment and work-up strategies. Our present study aimed to use a novel whole-brain high-resolution cardiovascular magnetic resonance imaging (WB-HRCMR) to assess both ICAS plaques and LSAs in recent stroke patients. METHODS: Twenty-nine symptomatic and 23 asymptomatic ICAS patients were enrolled in this study from Jan 2015 through Sep 2017 and all patients underwent WB-HRCMR. Intracranial atherosclerotic plaque burden, plaque enhancement volume, plaque enhancement index, as well as the number and length of LSAs were evaluated in two groups. Enhancement index was calculated as follows: ([Signal intensity (SI)plaque/SInormal wall on post-contrast imaging] - [SIplaque/SInormal wall on matched pre-contrast imaging])/(SIplaque / SInormal wall on matched pre-contrast imaging). Logistic regression analysis was used to investigate the independent high risk plaque and LSAs features associated with stroke. RESULTS: Symptomatic ICAS patients exhibited larger enhancement plaque volume (20.70 ± 3.07 mm3 vs. 6.71 ± 1.87 mm3 P = 0.001) and higher enhancement index (0.44 ± 0.08 vs. 0.09 ± 0.06 P = 0.001) compared with the asymptomatic ICAS. The average length of LSAs in symptomatic ICAS (20.95 ± 0.87 mm) was shorter than in asymptomatic ICAS (24.04 ± 0.95 mm) (P = 0.02). Regression analysis showed that the enhancement index (100.43, 95% CI - 4.02-2510.96; P = 0.005) and the average length of LSAs (0.80, 95% CI - 0.65-0.99; P = 0.036) were independent factors for predicting of stroke. CONCLUSION: WB-HRCMR enabled the comprehensive quantitative evaluation of intracranial atherosclerotic lesions and perforating arteries. Symptomatic ICAS had distinct plaque characteristics and shorter LSA length compared with asymptomatic ICAS.

Hyperintense Plaque on Intracranial Vessel Wall Magnetic Resonance Imaging as a Predictor of Artery-to-Artery Embolic Infarction.

BACKGROUND AND PURPOSE: The aim of the present study was to investigate atherosclerotic plaque characteristics in patients with artery-to-artery (A-to-A) embolic infarction by whole-brain high-resolution magnetic resonance imaging. METHODS: Seventy-four patients (mean age, 54.7±12.1 years; 59 men) with recent stroke in the territory of middle cerebral artery because of intracranial atherosclerotic disease were prospectively enrolled. Whole-brain high-resolution magnetic resonance imaging was performed in all the patients both precontrast and postcontrast administration by using a 3-dimensional T1-weighted vessel wall magnetic resonance imaging technique known as inversion-recovery prepared sampling perfection with application-optimized contrast using different flip angle evolutions. Patients were divided into A-to-A embolic infarction and non-A-to-A embolic infarction groups based on diffusion-weighted imaging findings. The characteristics of the intracranial atherosclerotic plaques were compared between groups. RESULTS: A total of 74 intracranial atherosclerotic plaques were analyzed (36 in A-to-A embolism group and 38 in non-A-to-A embolism group). Hyperintense plaques (HIPs) were more frequently observed in A-to-A embolism group (75.0% versus 21.1%; P<0.001). Eighteen of the 27 HIPs (66.7%) demonstrated hyperintense spots or areas located adjacent to the lumen versus 9 HIPs (33.3%) located within the plaque in A-to-A embolism group. Furthermore, a higher prevalence of plaque surface irregularity was also observed in A-to-A embolism group (41.7% versus 18.4%; P=0.029). Logistic regression analysis showed that HIP was the most powerful independent predictor of A-to-A embolic infarction (P<0.001), with the odds ratio of 11.2 (95% confidence interval, 3.5-36.2). CONCLUSIONS: A-to-A embolic infarction has distinct vulnerable plaque characteristics compared with non-A-to-A embolic infarction. HIP and plaque surface irregularity may predict A-to-A embolic infarction.

Lipoprotein-Associated Phospholipase A2 and Risk of Carotid Atherosclerosis and Cardiovascular Events in Community-Based Older Adults in China.

We explored the associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) level and carotid atherosclerosis with all phenotypes and cardiovascular disease (CVD) events in Chinese older adults. A total of 1257 adults aged ≥55 years who were free of CVD were enrolled in this cohort study. Lipoprotein-associated phospholipase A2 level was evaluated in 3 categories: Lp-PLA2 < 175, 175≤ Lp-PLA2 < 223, and Lp-PLA2 ≥ 223 ng/mL. The highest level of Lp-PLA2 was independently associated with common carotid artery intima-media thickening (≥1.0 mm; odds ratio [OR]: 1.60, 95% confidence interval [CI]: 1.14-2.26) and carotid plaque (OR: 1.42, 95% CI: 1.01-1.99) in individuals without carotid artery stenosis. At the end of the 5-year follow-up, after adjustment for CVD risk factors and carotid atherosclerosis status, Lp-PLA2 had remained an independent predictor for myocardial infarction (MI; hazard ratio [HR]: 1.90, 95% CI: 1.02-3.55) and CVD death (HR: 1.78, 95% CI: 1.02-3.13). However, no association was found with stroke. Therefore, elevated Lp-PLA2 level in the older adults studied was associated with an increased risk of carotid atherosclerosis and MI and CVD mortality. Lipoprotein-associated phospholipase A2 assessment might be used for MI and CVD death risk prediction.

Muscle edema of the lower limb determined by MRI in Asian hypokalaemic periodic paralysis patients.

OBJECTIVE: To determine the pattern of muscle edema occurring in the lower limb muscles of Asian hypokalaemic periodic paralysis (hypoPP) patients using magnetic resonance imaging (MRI). Specifically, the relationship between muscle edema and muscle activity during daily use was examined by comparing the lower limb muscle MRI of healthy subjects following exercise and hypoPP patients. METHODS: Twenty Asian patients (mean age: 29·3±7·53 years) clinically diagnosed with hypoPP were enrolled in the present study. Ten healthy subjects were also enrolled. Direct automated DNA sequencing of the S4 regions of CACNA1S and SCN4A in all hypoPP patients was performed. The upper and lower legs of all hypoPP patients during the time interval between attacks and healthy subjects pre- and post-exercise were examined on a 3 T system with T2-weighted fat saturation sequence. Images were evaluated by means of a region of interest analysis. A scoring from 0 to 3 was used to compare the degree of muscle edema among individual muscles. RESULTS: Three hypoPP patients were identified with mutations in the screened genes: R1239H and R900S of CACNA1S and R672H of SCN4A. The lower leg muscles of both hypoPP patients and healthy subjects after exercise displayed significantly higher MRI signal intensities compared to healthy subjects before exercise (P < 0·0001 and P < 0·0001, respectively). In contrast, there was no significant change in the upper leg muscle signal intensities of hypoPP patients and healthy subjects following exercise compared to pre-exercise healthy subjects (P  =  0·7598 and P  =  0·9651, respectively). In the hypoPP patient group, high signal intensity in the upper leg muscles was seen only in the patient with the R1239H mutation. In the lower legs, muscle edema was most frequently seen in the gastrocnemius lateralis, soleus, and gastrocnemius medialis in the hypoPP patient group. Furthermore, the degree of muscle edema was the greatest in these muscles. This similar pattern of muscle edema was also seen in healthy subjects after exercise. CONCLUSIONS: In Asian hypoPP patients, muscle edema as well as the underlying abnormal ion distributions across the muscle membrane is present even during the time interval between attacks of muscle weakness. The muscles of the lower leg are more likely to be edematous than muscles of the upper leg since these muscles are more actively used in daily life. Thus, muscles subjected to high activity are more likely to be edematous and sodium-overloaded.

Serum CRP and urinary trypsin inhibitor implicate postoperative cognitive dysfunction especially in elderly patients.

PURPOSE: Postoperative cognitive dysfunction (POCD) characterized as the decline of memory and executive function after major surgery is not well illustrated. The aim of this study is to discover whether inflammatory cytokines and urinary trypsin inhibitor (uTi) contribute to the development of POCD. METHOD: Sixty-three patients undergoing lumber discectomy and 47 age-matched control volunteers were involved in this study. The level of C-reaction protein (CRP) and uTi/urine creatinine (Ucr) was measured by immunoturbidimetry and enzyme-inhibition assay, respectively. Meanwhile, ELISA was involved to detect the level of IL-6, IL-10, MMP-9 in serum. Montreal Cognitive Assessment (MoCA) test was used to determine the cognitive decline of the patients and age-matched controls. RESULT: In POCD group, the level of IL-6, IL-10, CRP, MMP-9 in serum and uTi /Ucr in urine was significantly higher than that in the group without POCD. The POCD was more frequently observed in elderly group than in the middle-aged group (43.75% versus 19.35%, p = 0.038). After logistic regression analysis adjusted by the age, only serum CRP at 72 h postoperation and urinary uTi /Ucr at 24 h postoperation were the independent risk factors of POCD. CONCLUSION: Age-related increasing proinflammatory postoperation may result in higher occurrence of POCD in the elderly. Additionally, patients with extremely high concentrations of CRP in serum at 72 h postoperation and uTi /Ucr in urine at 24 h postoperation are more likely to experience POCD, especially in the elderly.

Association between clinical features and prognosis of patients with limb-shaking transient ischemic attack.

OBJECTIVE: This review aims to illustrate the relationship between clinical features and the prognosis of patients with limb-shaking transient ischemic attack (LS-TIA). DATA SOURCES: Relevant articles published in two main Chinese medical periodical databases (China National Knowledge Infrastructure and China Science Periodical Database) from 1986 to June 2013 were identified with keywords "limb shaking" and "transient ischemic attack". STUDY SELECTION: Original articles and case reports about LS-TIA were selected. RESULTS: A total of 63 cases collected from 19 articles were included in the pooled analysis. LS-TIA presented in two cerebrovascular diseases, of which atherosclerotic high-grade stenosis or occlusion in carotid artery system and moyamoya disease formed 95.2% and 4.8%, respectively. Of 63 patients, 11 (17.5%) were once misdiagnosed as epileptic and prescribed useless antiepilepsy drugs. The multivariable Logistic regression model showed a significant protective effect of patients with revascularization therapy on prognosis, compared with patients treated with drugs (odds ratio 0.20, 95% CI 0.05-0.74, P = 0.016). CONCLUSIONS: Chronic carotid artery system hypoperfusion can induce limb(s) shaking, followed by high possibility of ischemic stroke in the same brain territorial. Revascularization of the responsible artery may work better than conservative drug-based therapy.

Migraine-induced stroke with risk factors--involving two cerebral artery territories.

A patient with migraine-induced stroke with risk factors involving both anterior cerebral artery and posterior cerebral artery territory was presented. To better explain the symptom, the mechanisms of the migraine-induced stroke with risk factors were assessed and a hypothesis was raised.

[Correlation analysis of collateral circulation and clinical locations in patients with ischemic stroke].

OBJECTIVE: To study the correlation of compensation by collateral circulation and clinical locations in ischemic stroke cases. METHODS: A total of 25 ischemic stroke cases were retrospectively analyzed. MRI (magnetic resonance imaging) and DSA (digital subtraction angiography) were performed in all cases. Each patient was found to have at least one cerebral artery occlusion by DSA. The quantity relationship between collateral circulation and ischemic stroke location was analyzed by SPSS 11.5 statistics software. RESULTS: Among all cases, 46 arterial occlusions were found by chance. DSA demonstrated internal carotid artery occlusion (n = 24) and vertebral & basilar artery occlusion (n = 22). And all cases had at least one collateral circulation. Among 23 cases of single collateral circulation, there were 8 cases of single ischemic stroke locations and 15 cases of multiple ischemic stroke locations; among 23 cases of multiple collateral circulations, there were 18 cases of single ischemic stroke locations and 5 cases of multiple ischemic stroke locations. CONCLUSION: Effective collateral circulation can be established spontaneously through multiple ways when cerebral artery occlusion takes place if an intact Wills circle is present. Multiple collateral circulations may significantly decrease the quantity of ischemic stroke locations.

K+-dependent paradoxical membrane depolarization and Na+ overload, major and reversible contributors to weakness by ion channel leaks.

Normal resting potential (P1) of myofibers follows the Nernst equation, exhibiting about -85 mV at a normal extracellular K(+) concentration ([K(+)](o)) of 4 mM. Hyperpolarization occurs with decreased [K(+)](o), although at [K(+)](o) < 1.0 mM, myofibers paradoxically depolarize to a second stable potential of -60 mV (P2). In rat myofiber bundles, P2 also was found at more physiological [K(+)](o) and was associated with inexcitability. To increase the relative frequency of P2 to 50%, [K(+)](o) needed to be lowered to 1.5 mM. In the presence of the ionophore gramicidin, [K(+)](o) reduction to only 2.5 mM yielded the same effect. Acetazolamide normalized this increased frequency of P2 fibers. The findings mimic hypokalemic periodic paralysis (HypoPP), a channelopathy characterized by hypokalemia-induced weakness. Of myofibers from 7 HypoPP patients, up to 25% were in P2 at a [K(+)](o) of 4 mM, in accordance with their permanent weakness, and up to 99% were in P2 at a [K(+)](o) of 1.5 mM, in accordance with their paralytic attacks. Of 36 HypoPP patients, 25 had permanent weakness and myoplasmic intracellular Na(+) ([Na(+)](i)) overload (up to 24 mM) as shown by in vivo (23)Na-MRI. Acetazolamide normalized [Na(+)](i) and increased muscle strength. HypoPP myofibers showed a nonselective cation leak of 12-19.5 microS/cm(2), which may explain the Na(+) overload. The leak sensitizes myofibers to reduced serum K(+), and the resulting membrane depolarization causes the weakness. We postulate that the principle of paradoxical depolarization and loss of function upon [K(+)](o) reduction may apply to other tissues, such as heart or brain, when they become leaky (e.g., because of ischemia).

[R1239H mutation of CACNA1S gene in a Chinese family with hypokalaemic periodic paralysis].

OBJECTIVE: Mutation screening was performed to a Chinese family with hypokalaemic periodic paraiysis(HOKPP) for locating the corresponding mutations of gene and for specifying the clinical features associated with mutations. METHODS: The cilnical features of patients from HOKPP family were summurized. Techniques of target exon PCR and direct sequencing were used to screen the mutation in CACNA1S and SCN4A genes in all numbers of the family. RESULTS: Two patients of the family showed the typical features of HOKPP: the age of disease onset is during the childhood, acetazolamide is effective to patients treated. A heterozygous point mutation 3716 (G>A) causing R1239H was found in exon 30 of CACNA1S gene of the patients, but not found in normal members of the family. CONCLUSION: The mutant R1239H in CACNA1S gene exists in Chinese patients with familial hypokalaemic periodic paralysis.