Clinical significance of the Microbleed Anatomical Rating Scale score in ischemic stroke patients treated with intravenous thrombolysis.

BACKGROUND: Conflicting results were shown on the relationship between cerebral microbleeds (CMBs) burden and functional outcomes in patients treated with intravenous tissues plasminogen activator (IV tPA). We aimed to investigate the relationship between CMBs burden and functional outcomes using the Microbleed Anatomical Rating Scale (MARS) and determine its optimal cutoff value. METHODS: A retrospective study was conducted to include patients treated with IV tPA in our stroke center, and the MARS was used to assess the CMBs burden. Other clinical data including demographic factors, stroke severity, vascular risk factors, and clinical outcomes were also documented. Another mediation analysis was performed to investigate whether early neurological improvement could mediate the association between MARS and functional outcomes. RESULTS: A total of 408 patients were included. A cutoff value of 1.5 could predict functional outcomes in patients treated with IV tPA. Based on that cutoff value, MARS showed an independent relationship with functional outcomes [adjusted OR (Odds Ratio) 0.841, 95% confidence interval (CI) 0.720-0.982, P = .029]. A shift analysis showed that higher MARS score (MARS ≥1.5) was related with poor functional outcome according to mRS score distribution (OR = 0.519, 95% CI 0.336-0.803, P = .003). Total effect (indirect + direct effect) was calculated and showed in figure. Early neurological improvement mediated 24% of the effect of MARS score on functional outcomes. CONCLUSION: Our study showed that MARS could be a potential method to assess the functional outcome based on CMBs in patients treated with IV tPA, and MARS score ≥ 1.5 might be an optimal threshold for poor functional outcome.

Intravenous thrombolysis for acute ischemic stroke during two COVID-19 outbreaks in China: Wuhan pandemic and Beijing pandemic.

INTRODUCTION: The COVID-19 pandemic has had an impact on the emergency department (ED). Door-to-needle time (DNT) could be prolonged for intravenous thrombolysis (IVT) treatment. We aimed to investigate the impact of two COVID-19 pandemics on the workflow of IVT in our neurovascular ED. METHOD: We performed a retrospective analysis of patients who received IVT treatment in the neurovascular ED of Beijing Tiantan Hospital, Beijing, from January 20, 2020, to October 30, 2020, covering two COVID-19 pandemics in China. The time-based performances of IVT treatment including onset-to-arrival time, arrival-to-CT time, CT-to-needle time, door-to-needle time, and onset-to-needle time were recorded. Data on clinical characteristics and imaging information were also collected. RESULTS: Four hundred forty patients that received IVT were enrolled in this study. The number of patients admitted to our neurovascular ED began to decrease in December 2019 and was the lowest in April 2020 (n = 95). Longer DNT (Wuhan pandemic: 49.00 [35.00, 64.00] min; Beijing pandemic: 55.00 [45.50, 77.00] min) interval delays were observed during the two pandemics (p = .016). More patients admitted during the two pandemics had an 'unknown' subtype (Wuhan pandemic: 21.8%; Beijing pandemic: 31.4%. p = .008). The percentage of the cardiac embolism subtype was higher during the Wuhan pandemic (20.0%) than during other periods. The median admission NIHSS score increased during the Wuhan pandemic and the Beijing pandemic (8.00 [4.00, 12.00], 7.00 [4.50, 14.00], respectively, p < .001). CONCLUSION: The number of patients who received IVT decreased during the Wuhan pandemic. Higher admission NIHSS scores and prolonged DNT intervals were also observed during the Wuhan pandemic and the Beijing pandemic.

Prognostic value of glycemic gap in patients with spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Glycemic gap (GG), as a novel biomarker showing the acute glycemic change after the onset of acute illness, has been found to be associated with adverse outcomes in many diseases. This study aimed to explore the prognostic value of GG on long-term outcomes of spontaneous intracerebral hemorrhage (sICH). METHODS: The current study included 528 patients from a multicenter, prospective, consecutive, observational cohort study. Poor clinical outcome was defined as modified Rankin Scale ≥ 3. GG was calculated using admission blood glucose minus hemoglobin A1c-derived average blood glucose. Logistic regression analyses were performed to determine the association between GG and poor clinical outcomes at 30 days, 90 days, and 1 year. RESULTS: Glycemic gap was significantly associated with poor clinical outcomes at 30 days, 90 days, and 1 year (p < 0.05 for all models), where patients with higher GG were more likely to have poor clinical outcome. Restricted cubic splines revealed a positive association between GG and poor clinical outcome. In addition, patients with higher GG were more likely to have a higher 1-year mortality rate. The addition of GG to the intracerebral hemorrhage score improved the discrimination and calibration properties for the prediction of poor clinical outcome. CONCLUSIONS: Glycemic gap was independently associated with poor outcomes and may be a valuable prognostic factor in patients with sICH.

In-hospital clinical outcomes in diffusion weighted imaging-negative stroke treated with intravenous thrombolysis.

OBJECTIVE: We aimed to investigate whether negative diffusion weighted imaging (DWI) is related to the in-hospital clinical outcomes for ischemic stroke patients with intravenous tissues plasminogen activator (IV tPA). METHODS: We retrospectively enrolled patients who received IV tPA therapy within 4.5 hours from symptoms onset. The classification of DWI-positive or negative was based on post-IV tPA MR scan. Demographic factors, stroke characteristics, imaging information, and the in-hospital clinical outcomes including early neurological improvement (ENI) and favourable functional outcome were collected. Multivariable logistic regression and sensitivity analyses were conducted to test whether negative DWI imaging was an independent predictor of the in-hospital clinical outcomes. RESULTS: In the final study population, 437 patients treated with IV tPA were included and 12.36% of them had negative DWI imaging at the first MR scan post IV tPA. In the DWI-negative group, 51.9% (28/54) of the patients achieved ENI at 24 hours and 74.1% (40/54) of the patients achieved favourable clinical outcome at discharge. DWI-negative was not related to ENI (adjusted odds ratio 0.93, 95% confidence interval 0.17-4.91) or favourable clinical outcome (adjusted odds ratio 2.40, 95% confidence interval 0.48-11.95). Additional sensitivity analyses yielded similar results. CONCLUSION: DWI-negative is not associated with ENI or favourable functional outcome at discharge.

Characterisation of the relationships between rhythmic masticatory muscle activities and limb movements in patients with sleep bruxism.

BACKGROUND: Most rhythmic masticatory muscle activities (RMMAs) have been shown to be accompanied with limb movements (LMs) in sleep bruxism (SB) patients during sleep. OBJECTIVES: To compare the relationships between RMMAs and LMs in SB patients and normal subjects. METHODS: Polysomnographic recordings were performed on eight SB patients and nine normal subjects and the frequencies and durations of RMMAs as well as LMs were determined. Linear regression and correlation analysis were performed to study the relationship between durations of RMMAs and LMs when RMMAs occurred with LMs. RESULTS: Most LMs in SB patients, but not in normal subjects, were accompanied with RMMAs. RMMAs in SB patients were more likely to be isolated, phasic or mixed, while RMMAs in normal subjects were more likely to be tonic. The frequencies of LMs, isolated RMMAs and RMMAs accompanied with LMs in SB patients were significantly higher than those in normal subjects. Furthermore, linear regression and correlation analysis showed that duration of RMMAs was significantly associated with that of LMs when RMMAs occurred with LMs. The duration of RMMAs, when accompanied with LMs, in SB patients was significantly longer than that in normal subjects. CONCLUSIONS: Close relationships between LMs and RMMAs exist in SB patients and normal subjects, and SB episodes may be part of cortical arousal responses and the increased cortical activities associated with SB episodes may not just be localised to the central nervous system (CNS) that controls jaw movements but may also include other parts of CNS that controls LMs.

[Nutrients and Ecological Stoichiometry Characteristics of Typical Wetland Soils in the Lower Yellow River].

Carbon, nitrogen, phosphorus, and potassium in the soil are the necessary nutrient elements for plant growth, and their contents and ecological stoichiometry can reflect the status of soil quality and nutrient limitation. The Huayuankou Yellow River Floating Bridge Wetland in the lower Yellow River was selected as the research object. The methods of ANOVA, redundancy analysis, and linear regression fitting were used to study the contents of organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), total potassium (TK), alkaline nitrogen (AN), available phosphorus (AP), available potassium (AK), and their ecological stoichiometric ratios as well as the limiting elements of soil nutrients, and the key physicochemical properties that affect soil nutrients and their ecological stoichiometry in the wetland were revealed. The results showed that the mean values of ω(SOC), ω(TN), ω(TP), ω(TK), ω(AN), ω(AP), and ω(AK) in wetland soil were 5.46 g·kg-1, 0.60 g·kg-1, 0.28 g·kg-1, 17.06 g·kg-1, 13.75 mg·kg-1, 6.54 mg·kg-1, and 158.56 mg·kg-1, respectively, which showed an increasing trend from the river bank to the shoaly land and were generally higher at the high vegetation coverage areas than at the low vegetation coverage areas. There were significant correlations among SOC, TN, TP, and TK. Soil C/P, C/K, N/P, and N/K showed a consistent trend with soil nutrients, whereas C/N showed the opposite. The coefficients of variation of SOC, TN, AN, N/P, and N/K in the soil exceeded 50.00%, with significant spatial differences. The average value of C/N in wetland soil was 11.882, which was close to the average level of soils in China, whereas the average values of C/P and N/P were 49.119 and 4.516, respectively, both of which were lower than the average level of soils in China, and the N/P of soil was far less than 14, which indicated that N was limited in the soil. The proportion of clay and electrical conductivity combined to explain 61.4% and 43.9% of the variation in the soil nutrients and their ecological stoichiometry, respectively, which were the dominant soil physicochemical properties affecting the soil nutrients and their ecological stoichiometry of Huayuankou Yellow River Floating Bridge Wetland. The research results are helpful to improve our knowledge of nutrients and their influencing factors in the wetland soil of the lower Yellow River and provide an important scientific basis for the ecological restoration and management of the wetland in the lower Yellow River.

Application of Dual-Layer Spectral-Detector Computed Tomography Angiography in Identifying Symptomatic Carotid Atherosclerosis: A Prospective Observational Study.

BACKGROUND: Dual-layer spectral-detector dual-energy computed tomography angiography (DLCTA) can distinguish components of carotid plaques. Data on identifying symptomatic carotid plaques in patients using DLCTA are not available. METHODS AND RESULTS: In this prospective observational study, patients with carotid plaques were enrolled and received DLCTA. The attenuation for both polyenergetic image and virtual monoenergetic images (40, 70, 100, and 140 keV), as well as Z-effective value, were recorded in the noncalcified regions of plaques. Logistic regression models were used to assess the association between attenuations of DLCTA and the presence of symptomatic carotid plaques. In total, 100 participants (mean±SD age, 64.37±8.31 years; 82.0% were men) were included, and 36% of the cases were identified with the symptomatic group. DLCTA parameters were different between 2 groups (symptomatic versus asymptomatic: computed tomography [CT] 40 keV, 152.63 [interquartile range (IQR), 70.22-259.78] versus 256.78 [IQR, 150.34-408.13]; CT 70 keV, 81.28 [IQR, 50.13-119.33] versus 108.87 [IQR, 77.01-165.88]; slope40-140 keV, 0.91 [IQR, 0.35-1.87] versus 1.92 [IQR, 0.96-3.00]; Z-effective value, 7.92 [IQR, 7.53-8.46] versus 8.41 [IQR, 7.94-8.92]), whereas no difference was found in conventional polyenergetic images. The risk of symptomatic plaque was lower in the highest tertiles of attenuations in CT 40 keV (adjusted odds ratio [OR], 0.243 [95% CI, 0.078-0.754]), CT 70 keV (adjusted OR, 0.313 [95% CI, 0.104-0.940]), Z-effective values (adjusted OR, 0.138 [95% CI, 0.039-0.490]), and slope40-140 keV (adjusted OR, 0.157 [95% CI, 0.046-0.539]), with all P values and P trends <0.05. The areas under the curve for CT 40 keV, CT 70 keV, slope 40 to 140 keV, and Z-effective values were 0.64, 0.61, 0.64, and 0.63, respectively. CONCLUSIONS: Parameters of DLCTA might help assist in distinguishing symptomatic carotid plaques. Further studies with a larger sample size may address the overlap and improve the diagnostic accuracy.

Vasopressors and inotropes in cardiogenic shock patients: an analysis of the MIMIC-IV database.

Introduction: Pharmacological support has become the mainstay therapy in patients with cardiogenic shock (CS). Unfortunately, the clinical benefits of such potent drugs remain unclear, therefore, the present study aims to elucidate the safety and efficacy of vasoactive agents in CS patients. Methods: Medical Information Mart for Intensive Care (MIMIC) IV databases were used for this retrospective study. The primary outcome of this study was 30-day all-cause mortality. The subgroup analysis of was the relationship between the combined use of vasopressors and inotropes and 30-day all-cause mortality. Results: A total of 2,216 patients diagnosed with CS were enrolled in this study. The non-survivors group was more likely to be older, presented with chronic kidney disease, have a lower systolic blood pressure, lower heart rate, and higher respiratory rate (all p < 0.05). In the multivariate Cox regression analysis, only dopamine [HR (95%CI): 1.219 (1.003-1.482)], norepinephrine [HR (95%CI): 2.528 (1.829-3.493)], and milrinone [HR (95%CI): 0.664 (0.512-0.861)] remained an independent predictor for 30-day all-cause mortality. Furthermore, a subgroup analysis was performed and found that no statistically significant difference between no vasopressor/inotrope use and 1 vasopressor/inotrope use (p = 0.107). Meanwhile, a substantial deterioration of cumulative survival was observed when a combination of 2 or more vasopressors/inotropes was used in CS patients in comparison with no vasopressor/inotrope or only 1 vasopressor/inotrope use (all p < 0.05). Conclusions: Using vasopressors/inotropes agents was associated with a higher risk of 30-day all-cause mortality in CS patients. In addition, only milrinone was associated with a better prognosis among the available vasoactive agents.

Tenecteplase in Ischemic Stroke: Challenge and Opportunity.

Purpose of Review: Intravenous thrombolysis is the first-line therapy for ischemic stroke, and alteplase has been used as an intravenous thrombolysis drug for over 20 years. However, considering its low rate of recanalization and risk of intracerebral hemorrhage, alteplase may not be the optimal thrombolytic drug of choice for ischemic stroke. Tenecteplase (TNK) is a genetically engineered, mutant, tissue plasminogen activator that is a potential substitute to alteplase in ischemic stroke. The pharmacokinetic advantages of TNK include greater fibrin selectivity than alteplase and prolonged half-life time. In this review, we have summarized the clinical trials of TNK in ischemic stroke. Recent Findings: Clinical trials showed a higher recanalization rate of TNK over alteplase without increasing the rate of intracerebral hemorrhage. However, not all clinical trials showed superiority of TNK over alteplase in functional outcomes and early neurological improvement. TNK was superior to alteplase in terms of recanalization in patients who fulfilled the imaging mismatch criteria and in those planning to undergo mechanical thrombectomy. Summary: TNK has the potential to substitute alteplase for ischemic stroke therapy. Future TNK clinical trials that target functional outcomes are warranted.

Clinical Significance and Dynamic Change of Coagulation Parameters in Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

OBJECTIVE: Investigations on coagulation parameters including fibrinogen (Fbg), fibrinogen degradation products (FDP), and D-dimer in ischemic stroke patients treated with intravenous thrombolysis are insufficient. We aimed to investigate the association between in-hospital clinical outcomes and the coagulation parameters at different time points in ischemic stroke patients treated with intravenous tissues plasminogen activator (IV tPA). METHODS: We retrospectively enrolled patients who received IV tPA therapy within 4.5 h from symptoms onset. Demographics, clinical characteristics, imaging measures, and the discharge mRS score were collected. Multivariable logistic regression analyses were performed to test whether coagulation parameters were independent predictors for the in-hospital clinical outcomes. We also employed machine learning models to investigate whether coagulation parameters were able to improve the prediction of favorable functional outcomes. RESULTS: One hundred and fifty-two patients treated with IV tPA were included. Among the coagulation parameters, low D-dimers at 48 h proved to be an independent predictor of favorable functional outcome (adjusted odd ratio 0.24, 95% confidential intervals 0.06-0.92, P = 0.04). The AUC of D-dimer at 48 h to predict favorable functional outcome was 0.73 (0.60-0.87) and the optimal cut-off value was 0.92 (sensitivity 0.69, specificity 0.78). Machine learning models with D-dimer at 48 h had superior performance in predicting favorable functional outcomes and among the input variables in the machine learning models, D-dimer at 48 h showed the highest weight in predicting mRS 0-1 at discharge (38.44%). CONCLUSION: Increased levels of D-dimer at 48 h was associated with lower proportion of favorable functional outcomes in acute ischemic stroke patients with intravenous thrombolysis.

A novel method for quantifying human disturbances: A case study of Huaihe River Basin, China.

Human disturbances have become the main factors affecting the ecological environment. Therefore, evaluating the intensity of human disturbances is of great significance for ensuring effective regional conservation and ecosystem management. In this study, we constructed a novel method to quantify human disturbances based on three components of human disturbances into three types, namely naturalness transformation, natural resource consumption, and pollutant emissions. These components were quantified using the land use naturalness index (LNI), resource consumption index (RCI), and pollution emission index (PEI). Based on these three indicators, the human disturbances index (HDI) was calculated to reflect the intensity of human disturbances. In addition, remote sensing (RS), geographic information system (GIS), and multisource data were combined in the HDI method, taking into account the temporal variability of input parameters to achieve more convenient and comprehensive dynamic monitoring and evaluation of human disturbances. The applicability and effectiveness of the HDI method were assessed in the Huaihe River Basin, China. The obtained results revealed an increase and decrease in the intensities of human disturbances in the Huaihe River Basin from 1990 to 2005 and from 2010 to 2018, respectively. In addition, areas with a high level of human disturbances in the 1990-2005 period were mainly concentrated in the agricultural and industrial areas, while those in the 2010-2018 period were mainly observed in urban areas. This change was mainly due to a decrease in the pollutant emission amounts from agricultural and industrial lands and a marked increase in resource consumption in urban areas. This study provides theoretical guidance for regional conservation in the Huaihe River Basin and a new method for quantifying human disturbances.

Clinical Significance of Stress Hyperglycemic Ratio and Glycemic Gap in Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

Objective: The clinical significance of different glycemic parameters has been rarely investigated in ischemic stroke patients treated with intravenous tissue plasminogen activator (IV tPA). This study was aimed to investigate the association between different glycemic parameters and favorable functional outcome in patients treated with IV tPA. Methods: Patients with ischemic stroke who received IV tPA therapy at our stroke center were retrospectively enrolled. Four glycemic parameters were collected including admission glucose, HbA1c, stress hyperglycemia ratio (SHR) and glycemic gap (GG). Additional information was also recorded including demographics, medical history, stroke severity, imaging measures and mRS score at discharge. We used 5 machine learning models to investigate the predictive value of glycemic parameters. Results: Our study included 294 patients treated with IV tPA. SHR and GG were independently associated with favorable functional outcome (adjusted OR for SHR 0.03, 95% CI 0.01-0.72, P = 0.03; adjusted OR for GG 1.024, 95% CI 1.00-1.05, P = 0.04). Conclusion: SHR and GG were associated with functional outcomes in acute ischemic stroke patients with intravenous thrombolysis.

Association Between Neutrophil-to-Lymphocyte Ratio/Lymphocyte-to-Monocyte Ratio and In-Hospital Clinical Outcomes in Ischemic Stroke Treated with Intravenous Thrombolysis.

Objective: Investigations on neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) in patients with ischemic stroke are insufficient. We aimed to investigate the relationship of NLR and LMR with in-hospital clinical outcomes at different time points in ischemic stroke patients treated with intravenous tissues plasminogen activator (IV tPA). Methods: We retrospectively enrolled patients who received IV tPA therapy within 4.5 hours from symptoms onset. Demographics, clinical characteristics, imaging measures, and the in-hospital clinical outcomes including early neurological improvement (ENI, defined as NIHSS score reduction within 24 hours ≥4 points or decreased to the baseline) and favorable functional outcome (defined as modified Rankin scale 0-1) were collected. Multivariable logistic regression analyses were performed to test whether NLR or LMR was an independent predictor for the in-hospital clinical outcomes. Results: One hundred and two patients treated with IV tPA were included. NLR at 24 hours proved to be an independent predictor of ENI (adjusted OR=0.85, 95% CI=0.75-0.95, P=0.04). NLR at 48 hours and LMR at 48 hours proved to be independent predictors of mRS 0-1 at discharge (NLR at 48 hours: adjusted OR=0.64, 95% CI=0.49-0.83, P=0.01; LMR at 48 hours: adjusted OR=1.50, 95% CI=1.08-2.09, P=0.02). The AUC of NLR at 48 hours to predict favorable functional outcome at discharge was 0.79 (95% CI=0.70-0.88, P<0.001) and the optimal cut-off was 5.69 (sensitivity=0.52, specificity=0.63). Conclusion: In our study, NLR at 24 hours was correlated with ENI. Both NLR and LMR at 48 hours were closely associated with favorable functional outcomes at discharge.

Prior statin and short-term outcomes of primary intracerebral hemorrhage: From a large-scale nationwide longitudinal registry.

INTRODUCTION: The relationship between statins and intracerebral hemorrhage outcomes is unclear. AIM: We aimed to compare the in-hospital mortality and evacuation of intracranial hematoma rates in patients with primary intracerebral hemorrhage between prior statin users and nonusers. RESULTS: The final study population included 66,263 patients. Multivariable logistics analyses showed that prior statin use was not associated with in-hospital mortality for primary intracerebral hemorrhage (adjusted odd ratio 0.78, 95% CI 0.61-1.01), but reduced the proportion of patients undergoing evacuation of intracranial hematoma (adjusted odd ratio 0.70, 95% CI 0.61-0.82). Propensity score matching analyses yielded similar results. CONCLUSION: Prior statin use was not associated with in-hospital mortality but did reduce evacuation of intracranial hematoma rates.

Higher fasting blood glucose was associated with worse in-hospital clinical outcomes in patients with primary intracerebral hemorrhage: From a large-scale nationwide longitudinal registry.

INTRODUCTION: Studies that investigated the relationship between fasting blood glucose (FBG) and intracerebral hemorrhage (ICH) outcomes were insufficient. AIM: We aimed to investigate the association between FBG level and in-hospital clinical outcomes in patients with primary ICH. RESULTS: A total of 34,507 patients were enrolled in the final study. Compared with the reference group, the ≥6.1 and <7 mmol/L group showed nonsignificant higher in-hospital mortality (adjusted odds ratio [OR] 1.20, 95% confidence interval [CI] 0.69-2.11, p = 0.52), and a significant higher proportion of intracranial hematoma evacuation (adjusted OR 1.56, 95% CI 1.26-1.92, p < 0.001). The ≥7 mmol/L group showed both significant higher in-hospital mortality (adjusted OR 2.08, 95% CI 1.42-3.04, p = 0.52) and a significant higher proportion of intracranial hematoma evacuation (adjusted OR 2.09, 95% CI 1.78-2.47, p < 0.001). CONCLUSION: Higher FBG level was correlated with both higher mortality and proportion of evacuation of intracranial hematoma.

Heart rate changes associated with rhythmic masticatory muscle activities and limb movements in sleep bruxers: Preliminary findings.

Objective: To investigate the relationship of rhythmic masticatory muscle activities (RMMAs) and limb movements (LMs) with heart rate (HR) acceleration. Methods: The amplitude and duration of HR increases, the time to reach peak HR associated with RMMAs/LMs during sleep, duration of movement events, and their relationships with cortical arousal levels were determined in 9 sleep bruxers and 10 normal controls. Results: A total of 48.15% and 49.44% HR increased before the onset of RMMAs/LMs in the sleep bruxers and controls, respectively. All of the parameters of HR increases were significantly different between the sleep bruxers and the controls (p < 0.05-0.001) and between different cortical arousal levels (p < 0.01), and the duration of RMMAs/LMs was positively correlated with the parameters (Sleep bruxers: r2 = 0.18-0.88, p < 0.0001; Controls: r2 = 0.16-0.78, p < 0.0001). Discussion: These data suggest the HR increases are associated with the movement events and changes in cortical arousal levels in the sleep bruxers and controls. Abbreviations: LMs: Limb movements; HR: Heart rate; RMMAs: Rhythmic masticatory muscle activities; SB: Sleep bruxism; PSG: Polysomnographic; EEG: Electroencephalographic; PLMS: Periodic leg movements; SSRIs: Selective serotonin reuptake inhibitors; ECG: Electrocardiographic; EOG: Electrooculographic; EMG: Electromyographic; SD: Standard deviation; Fig: Figure; SEM: Standard error of mean; N1: Non-rapid eye movement sleep stage 1; N2: Non-rapid eye movement sleep stage 2; N3: Non-rapid eye movement sleep stage 3; REM: Rapid eye movement ; NA: No arousal; mAR: Microarousal; AW: Awakening.

Phase separation of Nur77 mediates celastrol-induced mitophagy by promoting the liquidity of p62/SQSTM1 condensates.

Liquid-liquid phase separation promotes the formation of membraneless condensates that mediate diverse cellular functions, including autophagy of misfolded proteins. However, how phase separation participates in autophagy of dysfunctional mitochondria (mitophagy) remains obscure. We previously discovered that nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) translocates from the nucleus to mitochondria to mediate celastrol-induced mitophagy through interaction with p62/SQSTM1. Here, we show that the ubiquitinated mitochondrial Nur77 forms membraneless condensates capable of sequestrating damaged mitochondria by interacting with the UBA domain of p62/SQSTM1. However, tethering clustered mitochondria to the autophagy machinery requires an additional interaction mediated by the N-terminal intrinsically disordered region (IDR) of Nur77 and the N-terminal PB1 domain of p62/SQSTM1, which confers Nur77-p62/SQSTM1 condensates with the magnitude and liquidity. Our results demonstrate how composite multivalent interaction between Nur77 and p62/SQSTM1 coordinates to sequester damaged mitochondria and to connect targeted cargo mitochondria for autophagy, providing mechanistic insight into mitophagy.

Retraction Note: minimally invasive versus open surgery for acute Achilles tendon rupture: a systematic review of overlapping meta-analyses.

Retraction Note: Li et al. Journal of Orthopaedic Surgery and Research (2016) 11:65 DOI https://doi.org/10.1186/s13018-016-0401-2.The authors have retracted this article [1] because of text overlap with a previously published article [2]. All authors agree to this retraction.

Increased chemosensitivity and radiosensitivity of human breast cancer cell lines treated with novel functionalized single-walled carbon nanotubes.

Hypoxia is a major cause of treatment resistance in breast cancer. Single-walled carbon nanotubes (SWCNTs) exhibit unique properties that make them promising candidates for breast cancer treatment. In the present study, a new functionalized single-walled carbon nanotube carrying oxygen was synthesized; it was determined whether this material could increase chemosensitivity and radiosensitivity of human breast cancer cell lines, and the underlying mechanisms were investigated. MDA-MB-231 cells growing in folic acid (FA) free medium, MDA-MB-231 cells growing in medium containing FA and ZR-75-1 cells were treated with chemotherapy drugs or radiotherapy with or without tombarthite-modified-FA-chitosan (R-O2-FA-CHI)-SWCNTs under hypoxic conditions, and the cell viability was determined by water-soluble tetrazolium salts-1 assay. The cell surviving fractions were determined by colony forming assay. Cell apoptosis induction was monitored by flow cytometry. Expression of B-cell lymphoma 2 (Bcl-2), survivin, hypoxia-inducible factor 1-α (HIF-1α), multidrug resistance-associated protein 1 (MRP-1), P-glycoprotein (P-gp), RAD51 and Ku80 was monitored by western blotting. The novel synthesized R-O2-FA-CHI-SWCNTs were able to significantly enhance the chemosensitivity and radiosensitivity of human breast cancer cell lines and the material exhibited its expected function by downregulating the expression of Bcl-2, survivin, HIF-1α, P-gp, MRP-1, RAD51 and Ku80.

Minimally invasive versus open surgery for acute Achilles tendon rupture: a systematic review of overlapping meta-analyses.

BACKGROUND: A number of meta-analyses have been carried out to evaluate the effects of minimally invasive surgery (MIS) versus open surgery (OS) for acute Achilles tendon rupture. However, discordant findings were seen in these meta-analyses. The present study, performing a systematic review of overlapping meta-analyses regarding MIS versus OS of acute Achilles tendon rupture, aimed to assist decision-makers interpret and choose among conflicting meta-analyses, as well as to offer treatment recommendations based on current best evidence. METHODS: The literature search was performed to identify systematic reviews comparing MIS with OS for Achilles tendon rupture. Meta-analyses only comprising randomized controlled trials (RCTs) were included. Two authors individually evaluated the quality of meta-analysis and extracted data. The Jadad decision algorithm was conducted to ascertain which meta-analysis offered the best evidence. RESULTS: A total of four meta-analyses was included. All these meta-analyses comprised RCTs or quasi-RCTs and were determined as Level-II evidence. The scores of the Assessment of Multiple Systematic Reviews (AMSTAR) ranged from 7 to 10 (median 9.5). The Jadad algorithm indicated that the best meta-analysis should be chosen according to the search strategies and application of selection. A high-quality meta-analysis with more RCTs was chosen, which suggested that there was no statistically significant difference between MIS and OS regarding rerupture rate, tissue adhesion, sural nerve injury, deep infection, and deep vein thrombosis. However, MIS could decrease superficial infection rate, and had a better patient satisfaction for good to excellent outcomes in comparison to OS. CONCLUSIONS: Based on the best available evidence, MIS may be superior to OS for treating acute Achilles tendon rupture. However, due to some limitations, this should be cautiously interpreted, and further high-quality studies are needed.