Exercise as the Key to Improve Cardiopulmonary Function in Patients with Valvular Heart Disease: A Systematic Review and Meta-Analysis.

Background: Valvular heart disease (VHD) is a type of cardiovascular disease with abnormal heart valve structure and/or function and a rapidly growing cause of global cardiovascular morbidity and mortality. Physical inactivity is a problem for patients with VHD, especially after surgery. However, there is no data on the effects of exercise on VHD from large multicentre randomised controlled trials (RCTs). Therefore, we conducted a systematic review and meta-analysis to provide a comprehensive analysis of small RCTs to evaluate the effects of exercise on cardiopulmonary function in patients with VHD and provide an evidence-based medicine basis for developing and guiding the clinical application of exercise in patients with VHD. Methods: We conducted a systematic review and meta-analysis of RCTs. We systematically searched electronic databases (PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure [CNKI], China Science and Technology Journal Database [VIP], WanFang Database, and SinoMed [CBM]) for all studies on exercise and VHD from their inception to January 2023. The quality of included studies was assessed using the Cochrane risk-of-bias tool. The primary outcomes were the six-minute walk test distance (6MWD), left ventricular ejection fraction (LVEF), and short-form 36-item health survey (SF-36). Results: This systematic review included 22 RCTs with 1520 subjects (869 men and 651 women). The meta-analysis results showed that exercise significantly improved exercise capacity measured by the 6MWD (mean difference [MD] = 25.54, 95% confidence interval [CI] = 19.98-31.11, I 2 = 0%, p < 0.00001), LVEF (MD = 6.20, 95% CI = 4.76-7.65, I 2 = 66%, p < 0.00001), and quality of life measured by the SF-36 (physical function: MD = 3.42, 95% CI = 2.12-4.72, I 2 = 12%, p < 0.00001; mental health: MD = 3.86, 95% CI = 0.52-7.20, I 2 = 68%, p = 0.020; social function: MD = 2.30, 95% CI = 0.64-3.97, I 2 = 45%, p = 0.007; bodily pain: MD = 2.60, 95% CI = 0.83-4.37, I 2 = 22%, p = 0.004) in patients with VHD compared to healthy controls. Conclusions: This study suggests that exercise can significantly improve cardiopulmonary function, enhance physical and social function, reduce bodily pain, and potentially improve mental health in patients with VHD, providing an evidence-based basis for better recovery in patients with VHD.

White matter hyperintensities induce distal deficits in the connected fibers.

White matter hyperintensities (WMH) are common in elderly individuals and cause brain network deficits. However, it is still unclear how the global brain network is affected by the focal WMH. We aimed to investigate the diffusion of WMH-related deficits along the connecting white matters (WM). Brain magnetic resonance imaging data and neuropsychological evaluations of 174 participants (aged 74 ± 5 years) were collected and analyzed. For each participant, WMH lesions were segmented using a deep learning method, and 18 major WM tracts were reconstructed using automated quantitative tractography. The diffusion characteristics of distal WM tracts (with the WMH penumbra excluded) were calculated. Multivariable linear regression analysis was performed. We found that a high burden of tract-specific WMH was related to worse diffusion characteristics of distal WM tracts in a wide range of WM tracts, including the forceps major (FMA), forceps minor (FMI), anterior thalamic radiation (ATR), cingulum cingulate gyrus (CCG), corticospinal tract (CST), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus-parietal (SLFP), superior longitudinal fasciculus-temporal (SLFT), and uncinate fasciculus (UNC). Furthermore, a higher mean diffusivity (MD) of distal tracts was linked to worse attention and executive function in the FMI, right CCG, left ILF, SLFP, SLFT, and UNC. The effect of WMH on the microstructural integrity of WM tracts may propagate along tracts to distal regions beyond the penumbra and might eventually affect attention and executive function.

Association of Admission NIHSS Score with Infarct Core Volume and Target Mismatch of Infarct Core/Penumbra Volume on CT Perfusion in Acute Ischaemic Stroke.

INTRODUCTION: Neurological impairment is associated with collateral status in acute ischaemic stroke (AIS). We aimed to validate the association between admission National Institutes of Health Stroke Scale (aNIHSS) score and infarct core volume (ICV) and target infarct core/penumbra volume mismatch (TMM) on CT perfusion (CTP) in AIS patients. METHODS: Patients with acute middle cerebral artery or internal carotid artery occlusion from 2011 to 2020 were included. All patients underwent pretreatment CTP at admission. ICV and TMM were analyzed with MIStar software on CTP maps. aNIHSS scores and clinical characteristics of patients were obtained from our prospectively recorded stroke database. RESULTS: We recruited 182 patients with a median age of 69.5 years; 85 (63.7%) were male, and the median aNIHSS score was 14. Of those, 149 (81.8%) had an ICV < 70 mL, and 139 (76.3%) had TMM. Lower aNIHSS was associated with an ICV < 70 mL, with an area under the curve (AUC) of 0.74, and TMM with an AUC of 0.76. Among all 15 items of the aNIHSS, the gaze score was the only item independently associated with an ICV < 70 mL (adjusted odds ratio [OR] = 0.42, 95% confidence interval [CI]: 0.22-0.79, p = 0.008) and TMM (adjusted OR = 0.5, 95% CI: 0.28-0.9, p = 0.021). One or both aNIHSS ≤ 16 and gaze score = 0 predicted TMM with a sensitivity of 0.79 and a specificity of 0.62. CONCLUSION: aNIHSS may be a useful tool to predict an ICV < 70 mL and TMM on CTP in AIS patients.

Comparison of methods between CT perfusion source images and CT angiography in collateral flow assessment.

BACKGROUND: The methods used for grading leptomeningeal collateral flow (LMF) on single-phase computed tomography angiography (CTA) are heterogeneous and limited by temporal resolution. PURPOSE: To compare the reliability of relative filling time delay (rFTD) on CT perfusion source images (CTP-SI) and the currently used single-phase CTA collateral assessment methods and evaluate their ability to predict clinical outcomes in acute ischemic stroke patients. MATERIAL AND METHODS: We analyzed consecutive middle cerebral artery or internal carotid artery occlusion patients who received multimodal CT before treatment and within 12 h of stroke symptom onset from October 2015 to December 2018. Patients were dichotomized using the 90-day mRS into good (0-1) versus adverse (2-6) outcomes. CTP-SI was used to identify the rFTD score. CTA images were reconstructed to assess collateral status using the collateral score (Cs) and region leptomeningeal collateral score (rLMCs). Two observers independently assessed images. RESULTS: The baseline characteristics (n = 54) were median age of 67 years and 68.5% of the participants were men. The baseline median NIHSS was 14. Good clinical outcomes were observed in 19 (35.2%) patients. The k value was higher for rFTDs (k = 0.779, P < 0.001) than Cs (k = 0.666, P < 0.001) and rLMCs (k = 0.763, P < 0.001). Higher rFTDs were correlated with lower rLMCs (Spearman's rho -0.68, P < 0.001) and Cs (rho -0.66, P < 0.001). In multivariate logistic regression, rFTD was associated with functional outcomes (P = 0.044). CONCLUSION: The rFTDs method is comparable to single-phase CTA-based assessments in assessing LMFs in acute ischemic stroke patients. Higher rFTDs is independently associated with adverse long-term functional outcomes.

Sodium ion transport across the endothelial glycocalyx layer under electric field conditions: A molecular dynamics study.

In the present research, the sodium ion transport across the endothelial glycocalyx layer (EGL) under an imposed electric field is investigated, for the first time, using a series of molecular dynamics simulations. The electric field is perpendicularly imposed on the EGL with varying strengths. The sodium ion molarity difference between the inner and outer layers of EGL, Δc, is used to quantify the sodium transport in the presence of the negatively charged glycocalyx sugar chains. Results suggest that a weak electric field increases Δc, regardless of whether the electric field is imposed perpendicularly inward or outward. By contrast, a strong electric field drives sodium ions to travel in the same orientation as the electric field. Scrutiny of the charge distribution of the glycocalyx sugar chains suggests that the electric field modifies the spatial layouts of glycocalyx atoms as it drives the transport of sodium ions. The modification in glycocalyx layouts further changes the inter-molecular interactions between glycocalyx sugar chains and sodium ions, thereby limiting the electric field control of ion transport. The sodium ions, in turn, alter the apparent bending stiffness of glycocalyx. Moreover, the negative charges of the glycocalyx sugar chains play an important role in maintaining structural stability of endothelial glycocalyx. Based on the findings, a hypothesis is proposed regarding the existence of a strength threshold of the electric field in controlling charged particles in the endothelium, which offers an alternative explanation for contrasting results in previous experimental observations.

Permeability Surface of Deep Middle Cerebral Artery Territory on Computed Tomographic Perfusion Predicts Hemorrhagic Transformation After Stroke.

BACKGROUND AND PURPOSE: Permeability surface (PS) on computed tomographic perfusion reflects blood-brain barrier permeability and is related to hemorrhagic transformation (HT). HT of deep middle cerebral artery (MCA) territory can occur after recanalization of proximal large-vessel occlusion. We aimed to determine the relationship between HT and PS of deep MCA territory. METHODS: We retrospectively reviewed 70 consecutive acute ischemic stroke patients presenting with occlusion of the distal internal carotid artery or M1 segment of the MCA. All patients underwent computed tomographic perfusion within 6 hours after symptom onset. Computed tomographic perfusion data were postprocessed to generate maps of different perfusion parameters. Risk factors were identified for increased deep MCA territory PS. Receiver operating characteristic curve analysis was performed to calculate the optimal PS threshold to predict HT of deep MCA territory. RESULTS: Increased PS was associated with HT of deep MCA territory. After adjustments for age, sex, onset time to computed tomographic perfusion, and baseline National Institutes of Health Stroke Scale, poor collateral status (odds ratio, 7.8; 95% confidence interval, 1.67-37.14; P=0.009) and proximal MCA-M1 occlusion (odds ratio, 4.12; 95% confidence interval, 1.03-16.52; P=0.045) were independently associated with increased deep MCA territory PS. Relative PS most accurately predicted HT of deep MCA territory (area under curve, 0.94; optimal threshold, 2.89). CONCLUSIONS: Increased PS can predict HT of deep MCA territory after recanalization therapy for cerebral proximal large-vessel occlusion. Proximal MCA-M1 complete occlusion and distal internal carotid artery occlusion in conjunction with poor collaterals elevate deep MCA territory PS.

The anti-atherosclerotic effect of tanshinol borneol ester using fecal metabolomics based on liquid chromatography-mass spectrometry.

Tanshinol borneol ester (DBZ) is a novel experimental compound that consists of two chemical structural units from danshensu and borneol. It exhibits efficacious anti-ischemic and anti-atherosclerosis activities in rats. A fecal metabolomics based on Liquid Chromatography-Mass Spectrometry combined with clinical histopathology and blood lipid estimation was employed to assess the efficacy and the metabolic changes caused by administration of DBZ in atherosclerotic rats. There were the typical pathological features of atherosclerosis and significantly increased levels of TC, TG and LDL-C in the atherosclerotic rat group. Nevertheless, atherosclerotic rats administered both DBZ (at a dose of 40 mg kg(-1)) and simvastatin (at a dose of 20 mg kg(-1)) showed good therapeutic effects. The results of the metabolomics studies showed that 55 differential metabolites such as sebacic acid, enterodiol, nonanedioic acid, dodecanedioic acid, cholic acid, 13(S)-HPODE, deoxycholic acid, some phosphatidylglycerol and phosphatidic acids were found, indicating that abnormal metabolism occurred in the pathways of fatty acid oxidation, linoleic acid metabolism, bile acid biosynthesis and glycerophospholipid metabolism in atherosclerotic rats. Compared to those in the model group, the contents of 41 differential metabolites showed a tendency to recover to a healthy level after DBZ administration. Metabolomics studies suggested that DBZ exhibited good treatment efficacy against atherosclerosis by adjusting disturbed metabolic pathways related to atherosclerosis. This study could provide an experimental basis for DBZ's application to act as a candidate drug with anti-atherosclerosis activity.

Higher Left Ventricle Mass Indices Predict Favorable Outcome in Stroke Patients with Thrombolysis.

BACKGROUND: We sought to assess the association of left ventricle mass (LVM) indices with the functional outcome of acute ischemic stroke (AIS) patients after intravenous tissue plasminogen activator (IV-tPA). METHODS: Consecutive AIS patients with IV-tPA were recruited. LVM indices including LVM/weight, LVM/surface, and LVM/heightˆ(2.7) on echocardiogram during hospitalization were retrospectively reviewed. Outcome was 90-day modified Rankin scale (mRS) scores. Multivariate logistic regression was performed to analyze the association of LVM indices with outcome. RESULTS: Between August 2010 and May 2014, 55 AIS patients (age range from 27 to 78 years, 69.1% men) with echocardiogram after thrombolysis were recruited. Lower baseline National Institutes of Health Stroke Scale (NIHSS; P = .009) and higher LVM indices (LVM/weight [P = .012], LVM/surface [P = .039], and LVM/heightˆ(2.7) [P = .045]) were significantly associated with 90-day favorable outcome (mRS, 0-2). In multivariate logistic regression analysis, LVM/weight independently predicted good outcome with an odds ratio of 3.89 (95% confidence interval, 1.05-14.42, P = .042) after adjustment for baseline NIHSS, onset-to-treatment time, hypertension, hemorrhagic transformation, and systolic left ventricle inner diameters. CONCLUSIONS: Higher LVM indices on echocardiogram are significantly associated with favorable outcome in stroke patients with IV-tPA, among which LVM/weight seems to be the most effective.

Higher fasting glucose next day after intravenous thrombolysis is independently associated with poor outcome in acute ischemic stroke.

BACKGROUND: We aimed to test the outcome-predictive power of routine fasting glucose (FG) obtained at second day after onset in intravenous thrombolysis (IVT) acute ischemic stroke (AIS) patients. METHODS: We identified AIS patients presenting to our institution between December 2011 and July 2013 within 4.5 hours of onset, who received admission glucose (AG) before IVT, FG, and glycated hemoglobin (HbA1c) the second day after admission, from our prospectively recorded stroke database. Multivariate logistic regression was used to assess the association of FG and 90-day modified Rankin Scale (mRS). RESULTS: Between December 2011 and July 2013, a total of 166 AIS patients received intravenous plasminogen activator. Of those, 119 patients who have AG before IVT, FG, and HbA1c the second day were included in the study. FG independently predicted 90-day clinical unfavorable outcome (mRS, 3-6 with an odds ratio of 1.576; 95% confidence interval [CI], 1.053-2.358; P = .027). This association was not significant in AG (P = .714), HbA1c (P = .655), and history of diabetes (P = .547). In receiver operating characteristic analysis, increased FG was associated with 90-day mRS (3-6) with an area under curve of .72, (95% CI, .65-.9; P = .001). CONCLUSIONS: FG is a powerful predictor associated with the outcome in IVT-treated AIS patients independent of AG and HbA1c.

Complete response after treatment of breast cancer with isolated liver metastasis: a case report.

Background: Breast cancer has a high incidence and is prone to metastasis, while isolated liver metastasis is rare. A growing body of evidence supports the effectiveness of treating breast cancer with anti-human epidermal growth factor receptor-2 (HER2) therapy in combination with chemotherapy. However, little is known about its impact on metastatic liver disease. There is also a lack of consensus on managing liver metastases from breast cancer, and no studies have been conducted on managing the disappearance of liver metastases after treatment. Case Description: In May 2021, a 51-year-old female patient with HER2-positive breast cancer with isolated liver metastases had immunohistochemistry of estrogen receptor (ER) (-), progesterone receptor (PR) (-), and HER2 (3+) for both her primary lesion and liver metastases. After undergoing 17 cycles of anti-HER2 therapy and chemotherapy, the patient expressed a desire for surgery. Then a preoperative examination was performed, which revealed the disappearance of both the primary breast lesion and the liver metastases. Immediately afterwards, a left mastectomy was performed, and postoperative pathology showed a complete response to the breast tumor. As for the liver, where the metastatic lesions disappeared, no relevant study has reported how to deal with this situation. Finally, after a hospital-wide discussion, the patient was given trastuzumab maintenance therapy. Until now, no obvious signs of recurrence or metastasis have been observed during regular follow-ups. Conclusions: This case suggests that maintenance therapy may be the best option for patients with breast cancer whose liver metastases disappear by medication. Also, it can be inferred that in HER2-positive metastatic breast cancer (MBC), patients with isolated liver metastases may be more likely to achieve a cure-like outcome. Nevertheless, more cases and follow-up information are needed to support these views.

CHinese Acute Tissue-Based Imaging Selection for Lysis In Stroke Tenecteplase II (CHABLIS-T II): rationale and design.

BACKGROUND AND PURPOSE: Tenecteplase (TNK) has demonstrated non-inferiority to alteplase in patients who had an acute ischaemic stroke presenting within 4.5 hours from symptom onset. The trial is aimed to explore the efficacy and safety of TNK in Chinese patients who had an acute ischaemic stroke with large/medium vessel occlusion in an extended time window. METHODS AND DESIGN: Chinese Acute Tissue-Based Imaging Selection for Lysis In Stroke Tenecteplase II (CHABLIS-T II) is a multicentre, prospective, block-randomised, open-label, blinded-endpoint, phase IIb study. Eligible patients are 1:1 randomised into two groups: 0.25 mg/kg TNK versus best medical management (excluding TNK). The safety and efficacy of 0.25 mg/kg TNK are assessed through reperfusion status and presence of symptomatic intracranial haemorrhage (sICH). STUDY OUTCOMES: The primary outcome is major reperfusion without sICH at 24-48 hours after randomisation. Major reperfusion is defined as restoration of blood flow to greater than 50% of the involved ischaemic territory assessed by catheter angiography or repeated perfusion imaging. Secondary outcomes include post-thrombolytic recanalisation, neurological improvements, change in the National Institutes of Health Stroke Scale score, haemorrhagic transformation at 24-48 hours, systematic bleeding at discharge, modified Rankin Scale (mRS) 0-1, mRS 0-2, mRS 5-6, mRS distribution and Barthel index at 90 days. DISCUSSION: CHABLIS-T II will provide important evidence of intravenous thrombolysis with TNK for patients who had an acute stroke in an extended time window.

Cerebral pulsatility in relation with various imaging markers of cerebral small vessel disease: a longitudinal community-based study.

Background: Cerebral pulsatility is thought to reflect arterial stiffness and downstream microvascular resistance. Although previous studies indicated cerebral pulsatility might closely relate to development of cerebral small vessel disease (SVD), yet evidence remain controversial and longitudinal data are rare. Objective: We aimed to explore relationships of cerebral pulsatility with severity and progression of various SVD imaging markers among the community-dwelling elderly. Design: A longitudinal cohort study. Methods: As part of the prospective community-based Shanghai Aging Study cohort, dementia- and stroke-free elderly were recruited for baseline assessment of cerebral pulsatility and SVD severity during 2010-2011 and traced for SVD progression during 2016-2017. Cerebral pulsatility was quantified for both anterior and posterior circulation with transcranial Doppler ultrasound. SVD imaging markers were measured with brain magnetic resonance imaging (MRI) including white matter hyperintensities (WMHs), enlarged perivascular spaces (ePVS), lacunes, and microbleeds. The cross-sectional and longitudinal relationships between cerebral pulsatility and SVD were analyzed by univariable and multivariable regression models. Results: Totally, 188 eligible subjects were included at baseline and out of them, 100 (53.19%) returned for a 7-year follow-up. At baseline, increased pulsatility of posterior circulation was independently associated with more periventricular WMH (PWMH) and ePVS in basal ganglia (BG-ePVS) but not with other SVD markers. Longitudinally, higher posterior pulsatility predicted greater PWMH progression in participants with hypertension (ß = 2.694, standard error [SE] = 1.112, p = 0.020), whereas pulsatility of anterior circulation was shown to prevent BG-ePVS progression among followed-up elderly (ß = -6.737, SE = 2.685, p = 0.012). However, no significant relationship was found between cerebral pulsatility and burden of lacunes or cerebral microbleeds. Conclusion: Higher pulsatility of posterior circulation could worsen PWMH progression, especially for participants with hypertension. But for development of ePVS, increased cerebral pulsatility could play a compensatory role among several healthy elderly. The distinct relationships between cerebral pulsatility and various SVD markers emphasized the importance of individualized SVD management.

Tenecteplase thrombolysis for stroke up to 24 hours after onset with perfusion imaging selection: the umbrella phase IIa CHABLIS-T randomised clinical trial.

BACKGROUND: The performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the promise of efficacy and safety of different doses of tenecteplase manufactured in China, in patients who had an acute ischaemic stroke with large/medium vessel occlusion beyond 4.5-hour time window. METHODS: The CHinese Acute tissue-Based imaging selection for Lysis In Stroke-Tenecteplase was an investigator-initiated, umbrella phase IIa, open-label, blinded-endpoint, Simon's two-stage randomised clinical trial in 13 centres across mainland China. Participants who had salvageable brain tissue on automated perfusion imaging and presented within 4.5-24 hours from time of last seen well were randomised to receive 0.25 mg/kg tenecteplase or 0.32 mg/kg tenecteplase, both with a bolus infusion over 5-10 s. The primary outcome was proportion of patients with promise of efficacy and safety defined as reaching major reperfusion without symptomatic intracranial haemorrhage at 24-48 hours after thrombolysis. Assessors were blinded to treatment allocation. All participants who received tenecteplase were included in the analysis. RESULTS: A total of 86 patients who had an acute ischaemic stroke identified with anterior large/medium vessel occlusion or severe stenosis were included in this study from November 2019 to December 2021. All of the 86 patients enrolled either received 0.25 mg/kg (n=43) or 0.32 mg/kg (n=43) tenecteplase, and were available for primary outcome analysis. Fourteen out of 43 patients in the 0.25 mg/kg tenecteplase group and 10 out of 43 patients in the 0.32 mg/kg tenecteplase group reached the primary outcome, providing promise of efficacy and safety for both doses based on Simon's two-stage design. DISCUSSION: Among patients with anterior large/medium vessel occlusion and significant penumbral mismatch presented within 4.5-24 hours from time of last seen well, tenecteplase 0.25 mg/kg and 0.32 mg/kg both provided sufficient promise of efficacy and safety. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04086147, https://clinicaltrials.gov/ct2/show/NCT04086147).

[Profiles of reproduction-related mRNA expressions in hypothalamus of female mice with advancing age].

OBJECTIVE: To explore the effects of aging on the levels of reproduction-related mRNA genes including Gnrh, KISS1/KISS1r, estrogen receptor-alpha (ERα), estrogen receptor-beta (ERß) and progesterone receptor (PR) in hypothalamus. METHODS: Proestrus and metestrus in young (3-4 months) and middle-aged (10-11 months) female mice and diestrus in senile (18-19 months) female mice were observed. And the levels of related mRNA genes in preoptic area anterior hypothalamus (POA-AH) and medial basal hypothalamus (MBH) were determined by real-time polymerase chain reaction (RT-PCR). RESULTS: In middle-aged mice on proestrus, the level of Gnrh mRNA in POA-AH (0.896 ± 0.049) was significantly lower than that in young mice (1.228 ± 0.147, P = 0.049). The level of ERα mRNA in POA-AH decreased in young mice on proestrus whereas increased in middle-aged mice (0.432 ± 0.063 vs 0.603 ± 0.018, P = 0.016). The level of ERα mRNA of POA-AH, both in middle-aged mice (0.432 ± 0.063, P = 0.014) and senile mice (0.403 ± 0.145, P = 0.020) on diestrus, were significantly lower than that in young mice. The PR mRNA expression in middle-aged mice on proestrus (1.037 ± 0.037) was markedly lower than that in young mice (1.251 ± 0.081, P = 0.031) . In senile mice, the levels of Gnrh mRNA (1.520 ± 0.146, P = 0.004) and ERß mRNA (1.572 ± 0.184, P = 0.011) increased in POA-AH compared with that in young mice on metestrus. Aging had no effect upon KISS1 and KISS1r mRNA levels in POA-AH. In contrast, KISS1 mRNA level of MBH in middle-aged (1.663 ± 0.398, P = 0.037) and senile (2.622 ± 0.454, P = 0.014) mice obviously increased compared with the young mice group. CONCLUSION: Higher levels of ERα mRNA and decreases of PR and Gnrh mRNA in POA-AH in middle-aged mice on proestrus may play an important role in declining reproductive function.

Reperfusion measurements, treatment time, and outcomes in patients receiving endovascular treatment within 24 hours of last known well.

AIMS: The aim of this study was to explore the interaction between reperfusion and treatment time on the outcomes of patients undergoing endovascular treatment presenting within 24 h of last known well, and to compare the predictive ability of different reperfusion measurements on outcomes. METHODS: Eligible patients from a single-center cohort were enrolled in this study. Reperfusion was assessed using reperfusion index (decreased volume of hypoperfusion lesion compared with baseline) measured by repeated perfusion imaging, and modified treatment in cerebral ischemia score measured by digital subtraction angiography, respectively. The interactions between reperfusion measurements and treatment time on outcomes were explored using multivariate-adjusted logistic and linear regression models. The predictive abilities of reperfusion measurements on outcomes were compared using area under the receiver operating characteristic curve (ROC-AUC) and values of R-square. RESULTS: Reperfusion index and treatment time had significant interactions on 3-month modified Rankin Scale (mRS) 0-2 and infarct growth (p for interaction <0.05). Although the AUCs were statistically similar (AUCs of mRS 0-2 prediction, mTICI≥2b:0.63, mTICI≥2c:0.59, reperfusion index≥0.5:0.66, reperfusion index ≥0.9:0.73, P value of any of the two AUCs >0.05), reperfusion index≥0.9 showed the highest R-square values in outcome prediction (R-square values of 3-month mRS 0-2 and infarct growth = 0.21) among all the reperfusion measurements. CONCLUSION: Treatment time mitigated the effect of reperfusion on outcomes of patients receiving endovascular treatment within 24 h of last known well. Reperfusion index≥0.9 might serve as a better proxy of good outcomes compared with other reperfusion measurements.

Integrative Bioinformatics Analysis Reveals CHEK1 and UBE2C as Luminal A Breast Cancer Subtype Biomarkers.

In light of the limited number of targetable oncogenic drivers in breast cancer (BRCA), it is important to identify effective and druggable gene targets for the treatment of this devastating disease. Herein, the GSE102484 dataset containing expression profiling data from 683 BRCA patients was re-analyzed using weighted gene co-expression network analysis (WGCNA). The yellow module with the highest correlation to BRCA progression was screened out, followed by functional enrichment analysis and establishment of a protein-protein interaction (PPI) network. After further validation through survival analysis and expression evaluation, CHEK1 and UBE2C were finally identified as hub genes related to the progression of BRCA, especially the luminal A breast cancer subtype. Notably, both hub genes were found to be dysregulated in multiple types of immune cells and closely correlated with tumor infiltration, as revealed by Tumor Immune Estimation Resource (TIMER) along with other bioinformatic tools. Construction of transcription factors (TF)-hub gene network further confirmed the existence of 11 TFs which could regulate both hub genes simultaneously. Our present study may facilitate the invention of targeted therapeutic drugs and provide novel insights into the understanding of the mechanism beneath the progression of BRCA.

Association of time to groin puncture with patient outcome after endovascular therapy stratified by etiology.

Background: Randomized clinical trials and large stroke registries have demonstrated a time-dependent benefit of endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). The aim of this study was to investigate whether this could be applied to different stroke subtypes in a real-world single-center cohort. Materials and methods: Consecutive ischemic stroke patients with LVOs presenting within 24 h after symptom onset were prospectively registered and retrospectively assessed. Baseline multimodal imaging was conducted before EVT. Independent predictors of functional independence [90-day modified Rankin scale (mRS), 0-2] and any incidence of intracranial hemorrhage (ICH) were explored using a stepwise logistic regression model in the entire cohort and in stroke subtypes. Results: From 2015 to 2020, 140 eligible patients received EVT, of whom 59 (42%) were classified as large artery atherosclerosis (LAA)-related. Time from last known normal to groin puncture was identified as an independent predictor for functional independence in patients of cardioembolic (CE) subtype [odds ratio (OR) 0.90 per 10 min; 95% CI 0.82-0.98; P = 0.013] but not in the LAA subtype and the whole cohort. Groin puncture within 6 h after the time of last known normal was associated with a lower risk of any ICH in the whole cohort (OR 0.36, 95% CI 0.17-0.75, P = 0.007). Sensitivity analysis of patients with complete imaging profiles also confirmed the above findings. Besides, compared with patients of the CE subtype, the LAA subtype had a smaller baseline ischemic core volume, a better collateral status, a slower core growth rate, and a numerically smaller final infarct volume. Conclusion: Faster groin puncture has a more pronounced effect on the functional outcome in patients of CE subtype than those of LAA subtype. Reducing time to groin puncture is of great importance in improving the prognosis of patients after EVT, especially those of CE subtype, and reducing the incidence of any ICH in all patients.

Poly(lactic-co-glycolic acid)-Chitosan-Gelatin Composite Nanomaterials for the Treatment of Diabetic Foot Ulcer Wound Infection.

In this experiment, a solid carrier was prepared with PLGA, gelatin, and chitosan as the main raw materials, so that BMSCs could exert their repairing effect directly in the ulcer area under the stimulation of Klotho protein. We chose to use electrospun PLGA as the main technical means to provide suitable adhesion growth environment for BMSCs by preparing PLGA nanofibers. At the same time, PLGA nanofibers are also a controlled release material, so that Klotho protein can remain active, thereby achieving the purpose of stimulating BMSCs for a long time. Through the nano-scale porous structure provided on the surface of the PLGA film, BMSCs can adhere well to the surface of the material and continuously receive stimulation from the inner Klotho protein. We applied this composite to mice with diabetic ulcers, and verified the effects of Klotho protein and BMSCs on DFU healing in five groups of mice. From the results, the Klotho+BMSCs group achieved the best healing effect, followed by the Klotho group alone, while the other three groups had no significant difference in healing effects. It is proved that both Klotho and BMSCs can help the healing of diabetic ulcers, but BMSCs alone cannot survive in harsh environments, and it is difficult to play a normal repair role. The purpose of this study was to investigate the effect of Klotho protein on BMSCs and ECs under high glucose conditions, and to find a suitable carrier for planting BMSCs on it. At the same time, the material also has a certain sustained release function. We have concluded that Klotho protein can promote the proliferation and migration of BMSCs and ECs under high glucose conditions. When combined with electrospinning technology to prepare a protein that can release Klotho, it also provides a microstructure suitable for BMSCs adhesion, thereby ensuring that BMSCs can successfully survive. In the end, we artificial Klotho protein can promote angiogenesis in diabetic ulcer areas by protecting BMSCs and ECs, thereby promoting healing of ulcer areas.

Research on the Treatment of Diabetic Foot with Ulcer Based on Nano-Silver Antibacterial Dressing.

The incidence of diabetes has been increasing year by year. Long-term growth in blood sugar causes complications such as diabetic foot ulcer and infections, which will increase the difficulty of ulcer treatment. The diabetes brings great pain and heavy economic burden to patients and their families. In view of the above problems, a nano-silver antibacterial dressing is synthesized in this paper to control bacterial infection on the ulcer surface and promote wound healing. This paper describes the preparation process and morphological characterization of nano-silver antibacterial dressings. 100 patients were selected, which divided into two groups for comparative experiments. The conventional group used conventional vaseline dressing, and the control group was nano-silver antibacterial dressing. The ulcer surface healing time, the number of dressing changes, and the control of infection were analyzed separately, and statistical analysis was performed with SPSS19.0. The experimental results are as follows. The use of nano-silver antibacterial dressing can significantly reduce the incidence of infection in diabetic foot patients, which is helpful to reduce the number of dressing changes, shorten the healing time of ulcer, and accelerate the turnover rate. It helps to shorten the course of diabetic foot, and it is recommended to promote its clinical application.