Low caveolin-1 levels and symptomatic intracranial haemorrhage risk in large-vessel occlusive stroke patients after endovascular thrombectomy.

BACKGROUND AND PURPOSE: Caveolin-1 (Cav-1) is reported to mediate blood-brain barrier integrity after ischaemic stroke. Our purpose was to assess the role of circulating Cav-1 levels in predicting symptomatic intracranial haemorrhage (sICH) amongst ischaemic stroke patients after endovascular thrombectomy (EVT). METHODS: Patients with large-vessel occlusive stroke after EVT from two stroke centres were prospectively included. Serum Cav-1 level was tested after admission. sICH was diagnosed according to the Heidelberg Bleeding Classification. RESULTS: Of 325 patients (mean age 68.6 years; 207 men) included, 47 (14.5%) were diagnosed with sICH. Compared with patients without sICH, those with sICH had a lower concentration of Cav-1. After adjusting for potential confounders, multivariate regression analysis demonstrated that the increased Cav-1 level was associated with a lower sICH risk (odds ratio 0.055; 95% confidence interval 0.005-0.669; p = 0.038). Similar results were obtained when Cav-1 levels were analysed as a categorical variable. Using a logistic regression model with restricted cubic splines, a linear and negative association of Cav-1 concentration was found with sICH risk (p = 0.001 for linearity). Furthermore, the performance of the conventional risk factors model in predicting sICH was substantially improved after addition of the Cav-1 levels (integrated discrimination index 2.7%, p = 0.002; net reclassification improvement 39.7%, p = 0.007). CONCLUSIONS: Our data demonstrate that decreased Cav-1 levels are related to sICH after EVT. Incorporation of Cav-1 into clinical decision-making may help to identify patients at a high risk of sICH and warrants further consideration.

Detecting prokaryote-specific gene and other bacterial signatures in thrombi from patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Microbial infection has been associated with thrombogenesis. This study aimed to detect bacterium-specific genes and other signatures in thrombi from patients with acute ischemic stroke and to relate these signatures to clinical characteristics. METHODS: Blood samples were collected before thrombectomy procedures, and thrombus samples were obtained during the procedure. Identification and classification of bacteria in the samples were accomplished using 16 S rRNA gene sequencing. Bacterium-specific structures were observed with transmission electron microscopy. Bacterium-specific biomarkers were detected through immunohistochemical staining. RESULTS: 16 S rRNA gene was detected in 32.1% of the thrombus samples from 81 patients. Bacillus (0.04% vs. 0.00046%, p = 0.003), Parabacteroides (0.20% vs. 0.09%, p = 0.029), Prevotella (1.57% vs. 0.38%, p = 0.010), Streptococcus (1.53% vs. 0.29%, p = 0.001), Romboutsia (0.18% vs. 0.0070%, p = 0.029), Corynebacterium (1.61% vs. 1.26%, p = 0.026) and Roseburia (0.53% vs. 0.05%, p = 0.005) exhibited significantly higher abundance in thrombi compared to arterial blood. Bacteria-like structures were observed in 22 (27.1%), while whole bacteria-like structures were observed in 7 (8.6%) thrombi under transmission electron microscopy. Immunohistochemical staining detected bacterium-specific monocyte/macrophage markers in 51 (63.0%) out of 81 thrombi. Logistic regression analysis indicated that alcohol consumption was associated with a higher bacteria burden in thrombi (odds ratio = 3.19; 95% CI, 1.10-9.27; p = 0.033). CONCLUSION: Bacterial signatures usually found in the oral cavity and digestive tract were detected in thrombi from patients with ischemic stroke. This suggests a potential involvement of bacterial infection in the development of thrombosis. Long-term alcohol consumption may potentially enhance this possibility.

Association between liver fibrosis and stroke recurrence in young patients with ischemic stroke.

BACKGROUND AND AIM: Stroke incidence rates are rising among young adults. Liver fibrosis has recently been recognized as a risk factor for cardiovascular events and stroke in the general population. It remains unclear whether liver fibrosis influences the prognosis of stroke. We aimed to evaluate the association between liver fibrosis and stroke recurrence in young stroke patients. METHODS AND RESULTS: Young adults with first-ever ischemic stroke were enrolled from a prospective stroke registry and were followed up for stroke recurrence. Liver fibrosis was evaluated by Fibrosis-4 (FIB-4) score and was stratified into three categories. Cox regression analysis was performed to assess the relationship between liver fibrosis and stroke recurrence. Over a median follow-up of 3.1 (1.7-4.6) years, 72 (11.6%) recurrent strokes occurred among 621 patients. According to the FIB-4 score, 73 (11.7%) patients had indeterminate fibrosis, while 11 (1.8%) had advanced fibrosis. Univariate Cox analysis revealed that patients with a high FIB-4 score were more likely to experience stroke recurrence than those with a low FIB-4 score (hazard ratio 3.748, 95% confidence interval 1.359-10.332, P = 0.011). After adjusting for potential confounders in the multivariate analysis, FIB-4 score remained an independent risk factor. CONCLUSIONS: Young stroke patients with advanced liver fibrosis were at a greater risk of stroke recurrence. Evaluating liver fibrosis may provide valuable information for stroke risk stratification, and the FIB-4 score could serve as a useful tool.

Lipocalin-2-mediated astrocyte pyroptosis promotes neuroinflammatory injury via NLRP3 inflammasome activation in cerebral ischemia/reperfusion injury.

BACKGROUND: Neuroinflammation is a vital pathophysiological process during ischemic stroke. Activated astrocytes play a major role in inflammation. Lipocalin-2 (LCN2), secreted by activated astrocytes, promotes neuroinflammation. Pyroptosis is a pro-inflammatory form of programmed cell death that has emerged as a new area of research in stroke. Nevertheless, the potential role of LCN2 in astrocyte pyroptosis remains unclear. METHODS: An ischemic stroke model was established by middle cerebral artery occlusion (MCAO) in vivo. In this study, in vitro, oxygen-glucose deprivation and reoxygenation (O/R) were applied to cultured astrocytes. 24p3R (the LCN2 receptor) was inhibited by astrocyte-specific adeno-associated virus (AAV-GFAP-24p3Ri). MCC950 and Nigericin sodium salt (Nig) were used to inhibit or promote the activation of NLRP3 inflammasome pharmacologically, respectively. Histological and biochemical analyses were performed to assess astrocyte and neuron death. Additionally, the neurological deficits of mice were evaluated. RESULTS: LCN2 expression was significantly induced in astrocytes 24 h after stroke onset in the mouse MCAO model. Lcn2 knockout (Lcn2-/-) mice exhibited reduced infarct volume and improved neurological and cognitive functions after MCAO. LCN2 and its receptor 24p3R were colocalized in astrocytes. Mechanistically, suppression of 24p3R by AAV-GFAP-24p3Ri alleviated pyroptosis-related pore formation and the secretion of pro-inflammatory cytokines via LCN2, which was then reversed by Nig-induced NLRP3 inflammasome activation. Astrocyte pyroptosis was exacerbated in Lcn2-/- mice by intracerebroventricular administration of recombinant LCN2 (rLCN2), while this aggravation was restricted by blocking 24p3R or inhibiting NLRP3 inflammasome activation with MCC950. CONCLUSION: LCN2/24p3R mediates astrocyte pyroptosis via NLRP3 inflammasome activation following cerebral ischemia/reperfusion injury.

Endothelial Dysfunction and Parenchymal Hematoma in Ischemic Stroke Patients after Endovascular Thrombectomy.

INTRODUCTION: Endothelial dysfunction (ED) may result in parenchymal injury and therefore worsen the outcomes of ischemic stroke. This study aimed to determine whether ED could predict parenchymal hematoma (PH) in ischemic stroke patients treated with endovascular thrombectomy (EVT). METHODS: Patients with large artery occlusion in the anterior circulation and treated with EVT were prospectively enrolled from 2 stroke centers. Serum soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-selectin, and von Willebrand factor (vWF) were tested and summed to a standardized score to reflect the levels of ED. PH was diagnosed according to the Heidelberg Bleeding Classification. RESULTS: Of the 325 enrolled patients (mean age, 68.6 years; 207 men), 41 (12.6%) developed PH. Patients with PH had higher concentrations of soluble E-selectin, vWF, and ED sum score. After adjusting for demographic characteristics, National Institutes of Health Stroke Scale score, pretreatment Alberta stroke program early computed tomography score, and other potential confounders, the increased ED burden was associated with PH (odds ratio, 1.432; 95% confidence interval, 1.031-1.988; p = 0.032). Similar significant results were found in the sensitivity analysis. The multiple-adjusted spline regression model showed a linear association between the total ED score and PH (p = 0.001 for linearity). Adding the ED score to the conventional model significantly improved the risk prediction of PH (net reclassification improvement = 25.2%, p = 0.001; integrated discrimination index = 2.9%; p = 0.001). CONCLUSIONS: This study demonstrated that ED might be related to PH. Introducing the ED score could increase the reliability of the PH risk model for stroke patients treated with EVT.

Extracellular vesicles carrying proinflammatory factors may spread atherosclerosis to remote locations.

Most cells involved in atherosclerosis release extracellular vesicles (EVs), which can carry bioactive substances to downstream tissues via circulation. We hypothesized that EVs derived from atherosclerotic plaques could promote atherogenesis in remote locations, a mechanism that mimics the blood metastasis of cancer. Ldlr gene knockout (Ldlr KO) rats were fed on a high cholesterol diet and underwent partial carotid ligation to induce local atherosclerosis. EVs were separated from carotid artery tissues and downstream blood of carotid ligation by centrifugation. MiRNA sequencing and qPCR were then performed to detect miRNA differences in EVs from rats with and without induced carotid atherosclerosis. Biochemical analyses demonstrated that EVs derived from atherosclerosis could increase the expression of ICAM-1, VCAM-1, and E-selectin in endothelial cells in vitro. EVs derived from atherosclerosis contained a higher level of miR-23a-3p than those derived from controls. MiR-23a-3p could promote endothelial inflammation by targeting Dusp5 and maintaining ERK1/2 phosphorylation in vitro. Inhibiting EV release could attenuate atherogenesis and reduce macrophage infiltration in vivo. Intravenously administrating atherosclerotic plaque-derived EVs could induce intimal inflammation, arterial wall thickening and lumen narrowing in the carotids of Ldlr KO rats, while simultaneous injection of miR-23a-3p antagomir could reverse this reaction. The results suggested that EVs may transfer atherosclerosis to remote locations by carrying proinflammatory factors, particularly miR-23a-3p.

The prognostic value of caveolin-1 levels in ischemic stroke patients after mechanical thrombectomy.

BACKGROUND AND PURPOSE: The impact of serum caveolin-1 (Cav-1) on clinical outcomes in patients after mechanical thrombectomy (MT) is unclear. We aimed to investigate the association between serum cav-1 levels and the 3-month functional outcome. METHODS: We prospectively enrolled and analyzed patients with an anterior circulation large vessel occlusion who underwent MT. Serum cav-1 concentrations were tested after admission. The primary outcome was a 90-day modified Rankin Scale score of 3-6. RESULTS: Of the 237 recruited patients (mean age, 69.7 ± 12.1 years; 152 male), 131 (55.3%) experienced a 90-day poor outcome. After adjustment for demographic characteristics and other covariates, patients with higher serum Cav-1 levels had a reduced risk of poor outcome at 3 months (Per 1-standard deviation increase; odd ratios [OR], 0.59; 95% confidence interval [CI], 0.39 - 0.89, P = 0.013). Elevated Cav-1 concentrations (Per 1-standard deviation increase; OR, 0.59; 95% CI, 0.40 - 0.88, P = 0.011) were significantly associated with a favorable shift in modified Rankin Scale score distribution. Similar results were confirmed when the Cav-1 levels were analyzed as a categorical variable. Furthermore, the restricted cubic spline showed a linear association between Cav-1 levels and 90-day poor outcome (P = 0.032 for linearity). CONCLUSIONS: Increased serum Cav-1 levels were associated with improved prognosis at 3 months in ischemic stroke patients after MT, suggesting that Cav-1 may be a potential prognostic biomarker for ischemic stroke after reperfusion therapy.

The metabolic score for insulin resistance as a predictor of clinical outcome in stroke patients treated by intravenous thrombolysis.

BACKGROUND AND PURPOSE: Insulin resistance is associated with clinical outcomes among patients with ischemic stroke. We aimed to investigate the association between metabolic score for insulin resistance (METS-IR) and clinical outcomes in stroke patients treated by intravenous thrombolysis (IVT). METHODS: We recruited participants treated with IVT from a prospective registry including 3 stroke centers. Poor outcome was defined as a modified Rankin scale score ≥ 3 points at 90 days after the index stroke. We performed logistic regression models to investigate the association between METS-IR and the risk of poor outcome. We used the receiver operative characteristic to assess the discriminative ability and the restricted cubic spline to explore the relationship between METS-IR and the poor outcome. RESULTS: This study enrolled a total of 1074 patients (median age, 68; 63.8% male). Three hundred sixty (33.5%) patients had poor outcome after IVT. METS-IR was associated with the risk of the poor outcome with the increase of confounding factors in models (odds ratio [OR], 1.078; 95% confidence interval [CI], 1.058-1.099; P < 0.001). The area under the curve for METS-IR for predicting the poor outcome was 0.790 (95% CI, 0.761-0.819). The restricted cubic spline revealed an increasing and non-linear association between METS-IR and the poor outcome (P for non-linearity < 0.001). CONCLUSION: Our study found that METS-IR was associated with an increased risk of poor outcome after IVT. Further studies are warranted to investigate the efficacy of anti-diabetic agents regarding IR on clinical outcomes after IVT.

Rational number harmonic mode-locked dual-loop optoelectronic oscillator with low supermode noise and low intermodulation distortions.

A rational number harmonic mode-locked dual-loop optoelectronic oscillator (RHML-DL-OEO) is proposed and experimentally demonstrated. In the proposed system, an external radio frequency (RF) signal and a feedback oscillating microwave signal drive two arms of a dual-drive Mach-Zehnder modulator (DMZM). Mode locking is realized by frequency detuning. The larger effective free spectrum range (FSR) and higher side-mode suppression result from the Vernier effect effectively suppress supermode noise and intermodulation distortions (IMDs). Experimental results demonstrate that the microwave frequency comb (MFC) signals with repetition frequencies of 901.8 kHz, 2.3046 MHz and 5.3106 MHz are generated by 9th-, 23rd- and 53rd-order rational number harmonic mode-locking, respectively. Compared with the rational number harmonic mode-locked optoelectronic oscillator based on single-loop structure, the supermode noise suppression ratios of the scheme we propose are improved by 30.5 dB, 27.6 dB and 20.3 dB, respectively. Furthermore, the performance of single sideband (SSB) phase noise is also investigated.

Non-alcoholic fatty liver disease and stroke: A Mendelian randomization study.

BACKGROUND: The association between non-alcoholic fatty liver disease (NAFLD) and the risk of stroke is heterogeneous. Therefore, we aimed to examine any potential causal relationship between these two traits through Mendelian randomization. METHODS: The genetic instruments associated with NAFLD were selected from a large genome-wide association study in individuals of European ancestry (1483 cases and 17,781 controls, replicated in 559 cases and 945 controls). The genetic associations for stroke (40,585 cases and 406,111 controls) and ischemic stroke (34,217 cases and 406,111 controls) were selected from the MEGASTROKE consortium of European ancestry participants. The causal effects on ischemic stroke subtypes, including large artery atherosclerosis (LAA) (4373 cases and 146,392 controls), small vessel occlusion (SVO) (5386 cases and 192,662 controls), and cardioembolic stroke (7193 cases and 204,570 controls), were also analyzed. The inverse variant weighted method was performed to obtain the casual estimates. Heterogeneity and pleiotropy of individual single nucleotide polymorphisms were also tested for the robustness of the results. RESULTS: NAFLD was not associated with stroke (odds ratio [OR] 1.015; 95% confidence interval [CI] 0.996-1.034; p = 0.121) and ischemic stroke (OR 1.017; 95% CI 0.997-1.037; p = 0.092). Regarding ischemic stroke subtypes, there were positive causal inferences on LAA (OR 1.065; 95% CI 1.004-1.129; p = 0.037) and SVO (OR 1.058; 95% CI 1.003-1.116; p = 0.037), while it was not significant for cardioembolic stroke (OR 1.026; 95% CI 0.983-1.071; p = 0.243). CONCLUSION: This study suggests that the potential causal effect of NAFLD on ischemic stroke may be confined to the LAA and SVO subtypes.

The association of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and lymphocyte to monocyte ratio with post-thrombolysis early neurological outcomes in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: To investigate the association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) with post-thrombolysis early neurological outcomes including early neurological improvement (ENI) and early neurological deterioration (END) in patients with acute ischemic stroke (AIS). METHODS: AIS patients undergoing intravenous thrombolysis were enrolled from April 2016 to September 2019. Blood cell counts were sampled before thrombolysis. Post-thrombolysis END was defined as the National Institutes of Health Stroke Scale (NIHSS) score increase of ≥ 4 within 24 h after thrombolysis. Post-thrombolysis ENI was defined as NIHSS score decrease of ≥ 4 or complete recovery within 24 h. Multinomial logistic regression analysis was performed to explore the relationship of NLR, PLR, and LMR to post-thrombolysis END and ENI. We also used receiver operating characteristic curve analysis to assess the discriminative ability of three ratios in predicting END and ENI. RESULTS: Among 1060 recruited patients, a total of 193 (18.2%) were diagnosed with END and 398 (37.5%) were diagnosed with ENI. Multinomial logistic model indicated that NLR (odds ratio [OR], 1.385; 95% confidence interval [CI] 1.238-1.551, P = 0.001), PLR (OR, 1.013; 95% CI 1.009-1.016, P = 0.001), and LMR (OR, 0.680; 95% CI 0.560-0.825, P = 0.001) were independent factors for post-thrombolysis END. Moreover, NLR (OR, 0.713; 95% CI 0.643-0.791, P = 0.001) served as an independent factor for post-thrombolysis ENI. Area under curve (AUC) of NLR, PLR, and LMR to discriminate END were 0.763, 0.703, and 0.551, respectively. AUC of NLR, PLR, and LMR to discriminate ENI were 0.695, 0.530, and 0.547, respectively. CONCLUSIONS: NLR, PLR, and LMR were associated with post-thrombolysis END. NLR and PLR may predict post-thrombolysis END. NLR was related to post-thrombolysis ENI.

Noncoding RNAs involved in DNA methylation and histone methylation, and acetylation in diabetic vascular complications.

Diabetes is a metabolic disorder and its incidence is still increasing. Diabetic vascular complications cause major diabetic mobility and include accelerated atherosclerosis, nephropathy, retinopathy, and neuropathy. Hyperglycemia contributes to the pathogenesis of diabetic vascular complications via numerous mechanisms including the induction of oxidative stress, inflammation, metabolic alterations, and abnormal proliferation of EC and angiogenesis. In the past decade, epigenetic modifications have attracted more attention as they participate in the progression of diabetic vascular complications despite controlled glucose levels and regulate gene expression without altering the genomic sequence. DNA methylation and histone methylation, and acetylation are vital epigenetic modifications and their underlying mechanisms in diabetic vascular complication are still urgently needed to be investigated. Non-coding RNAs (nc RNAs) such as micro RNAs (miRNAs), long non-coding RNA (lncRNAs), and circular RNAs (circ RNAs) were found to exert transcriptional regulation in diabetic vascular complication. Although nc RNAs are not considered as epigenetic components, they are involved in epigenetic modifications. In this review, we summarized the investigations of non-coding RNAs involved in DNA methylation and histone methylation and acetylation. Their cross-talks might offer novel insights into the pathology of diabetic vascular complications.

Delayed Stroke Treatment during COVID-19 Pandemic in China.

BACKGROUND: Social distance, quarantine, pathogen testing, and other preventive strategies implemented during CO-VID-19 pandemic may negatively influence the management of acute ischemic stroke (AIS). OBJECTIVE: The current study aimed to evaluate the impacts of COVID-19 pandemic on treatment delay of AIS in China. METHODS: This study included patients with AIS admitted in 2 hospitals in Jiangsu, China. Patients admitted before and after the COVID-19 pandemic outbreak (January 31, 2020, as officially announced by the Chinese government) were screened to collect sociodemographic data, medical history information, and symptom onset status from clinical medical records and compared for pre- (measured as onset-to-door time [ODT]) and posthospital delay (measured as door-to-needle time [DNT]). The influencing factors for delayed treatment (indicated as onset-to-needle time >4.5 h) were analyzed with multivariate logistic regression analysis. RESULTS: A total of 252 patients were included, of which 153 (60.7%) were enrolled before and 99 (39.3%) after the COVID-19 pandemic. ODT increased from 202 min (interquartile range [IQR] 65-492) before to 317 min (IQR 75-790) after the COVID-19 pandemic (p = 0.001). DNT increased from 50 min (IQR 40-75) before to 65 min (IQR 48-84) after the COVID-19 pandemic (p = 0.048). The proportion of patients with intravenous thrombolysis in those with AIS was decreased significantly after the pandemic (15.4% vs. 20.1%; p = 0.030). Multivariate logistic regression analysis indicated that patients after COVID-19 pandemic, lower educational level, rural residency, mild symptoms, small artery occlusion, and transported by other means than ambulance were associated with delayed treatment. CONCLUSIONS: COVID-19 pandemic has remarkable impacts on the management of AIS. Both pre- and posthospital delays were prolonged significantly, and proportion of patients arrived within the 4.5-h time window for intravenous thrombolysis treatment was decreased. Given that anti-COVID-19 measures are becoming medical routines, efforts are warranted to shorten the delay so that the outcomes of stroke could be improved.

Predictors of mortality for acute vertebrobasilar artery occlusion receiving endovascular treatment.

OBJECTIVES: Acute vertebrobasilar artery occlusion (VBAO) is a devastating type of stroke with a high mortality rate. This study aimed to investigate the predictors of 3-month and 1-year mortality in VBAO patients receiving endovascular treatment (EVT). MATERIALS & METHODS: Consecutive acute VBAO patients undergoing EVT between January 2014 and December 2019 were retrospectively analyzed in a prospectively maintained database. Multivariate logistical regression models were used to explore the potential predictors of mortality at 3 months and 1 year, respectively. The discrimination of the final model was assessed with the area under the receiver operating characteristic curve. RESULTS: A total of 100 patients were enrolled in this study (mean age 62 years; 77.0% male). After excluding patients lost to follow-up, the overall mortality rate was 34.3% (34/99) at 3 months and 45.4% (44/97) at 1 year. The Glasgow Coma Scale (GCS) score at 24 h (Odds ratio [OR], 0.676; 95% confidence interval [CI], 0.540-0.846; p = .001) and mechanical ventilation (MV) (OR, 7.356; 95% CI, 2.200-24.593; p = .001) were predictors of 3-month mortality after adjusting for potential confounders in multivariable analysis. Furthermore, the GCS score at 24 h (OR, 0.714; 95% CI, 0.590-0.864; p = .001), intracranial hemorrhage (OR, 7.330; 95% CI, 1.772-30.318; p = .006), and MV (OR, 5.804; 95% CI, 1.841-18.294; p = .003) were independently associated with mortality at 1 year. Sensitivity analyses showed similar results. CONCLUSION: The 24-h GCS score and MV were common predictors of 3-month and 1-year mortality, and ICH was an additional predictor of 1-year mortality.

Modified colonic transit test in healthy subjects and constipated patients: A triple-phase, two-center prospective study.

BACKGROUND AND AIM: Classic daily-ingestion single-film protocol using radiopaque markers for colonic transit time (CTT) is unsuitable for Chinese patients because of rapid colonic motility. A new modified method needs to be established. METHODS: The triple-phase study was performed. In Phase I, the classic protocol was assessed to evaluate its feasibility for Chinese subjects. In Phase II, a modified protocol was performed in two centers on 180 healthy subjects and 90 constipated patients to determine optimal conditions. In Phase III, the simplified protocol was validated on 90 constipated patients. RESULTS: All the subjects of the Phase I expelled more than 95% of the markers during the examination period, which means that the classic protocol is unsuitable for Chinese patients. The 20.9-h mean total CTT for healthy Chinese subjects was much faster than that seen in Western countries. As shown by Phase II, the numbers of subjects went beyond the upper limit were 22 in P1TCTT and 10 in P2TCTT (8.14% vs 3.70%, P = 0.029). The percentage of values fall outside of the measurement range of excretion ratio was around half of our study subjects (45-70%), whereas this percentage was only 3.70% using P2TCTT. The simplified protocol had a diagnostic accuracy for constipation of 0.81, with a sensitivity and specificity of 0.46 and 0.97, respectively. CONCLUSIONS: Colon movement in Chinese individuals is significantly faster than that of Western populations. The modified protocol generated in this study is appropriate for diagnosis of constipation in population with rapid colon motility.

CircRNA RSF1 regulated ox-LDL induced vascular endothelial cells proliferation, apoptosis and inflammation through modulating miR-135b-5p/HDAC1 axis in atherosclerosis.

BACKGROUND: Atherosclerosis (AS) is the most common type in cardiovascular disease. Due to its complex pathogenesis, the exact etiology of AS is unclear. circRNA has been shown to play an essential role in most diseases. However, the underlying mechanism of circRNA in AS has been not understood clearly. METHODS: Quantitative Real-Time PCR assay was used to detect the expression of circRSF1, miR-135b-5p and histone deacetylase 1 (HDAC1). Western blot was applied to the measure of protein expression of HDAC1, B-cell lymphoma-2 (Bcl-2), BCL2-associated X (Bax), cleaved-caspase-3, vascular cell adhesion molecule 1 (VCAM1), intercellular cell adhesion molecule-1 (ICAM1) and E-selectin. MTT assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Dual luciferase reporter assay and RIP assay was used to determine the relationship among circRSF1, miR-135b-5p and HDAC1. Besides, an ELISA assay was performed to measure the levels of IL-1ß, IL-6, TNF-α and IL-8. RESULTS: In this study, ox-LDL inhibited circRSF1 and HDAC1 expression while upregulated miR-135b-5p expression in Human umbilical vein endothelial cells (HUVECs). Importantly, ox-LDL could inhibit HUVECs growth. Moreover, promotion of circRSF1 or inhibition of miR-135b-5p induced cell proliferation while inhibited apoptosis and inflammation of ox-LDL-treated HUVECs, which was reversed by upregulating miR-135b-5p or downregulating HDCA1 in ox-LDL-treated HUVECs. More than that, we verified that circRSF1 directly targeted miR-135b-5p and HDAC1 was a target mRNA of miR-135b-5p in HUVECs. CONCLUSION: CircRSF1 regulated ox-LDL-induced vascular endothelial cell proliferation, apoptosis and inflammation through modulating miR-135b-5p/HDAC1 axis in AS, providing new perspectives and methods for the treatment and diagnosis of AS.

INF2 p.Arg214Cys mutation in a Chinese family with rapidly progressive renal failure and follow-up of renal transplantation: case report and literature review.

BACKGROUND: Heterozygous mutations in the inverted formin 2 (INF2) gene are related to secondary focal segmental glomerulosclerosis (FSGS), a rare secondary disease associated with rapidly progressive renal failure. CASE PRESENTATION: We report a patient with familial autosomal INF2 mutation manifesting nephritic syndromes and elevated serum creatinine levels. Mutational analysis revealed an autosomal dominant (AD) inheritance pattern and a mutation in exon 4 (p.Arg214Cys) of INF2 as the likely cause, which has not been previously described in an Asian family. The patient progressed to end-stage renal disease (ESRD) and received hemodialysis. His mother had undergone renal transplant 3 years earlier, and his grandmother had carried the p.Arg214Cys mutation for more than 80 years without any sign of renal dysfunction. CONCLUSIONS: This is the first report to identify an association between a familial autosomal dominant INF2 p.Arg214Cys mutation and rapidly progressive renal disease in an Asian family. INF2 mutation analysis should not be restricted to individuals without family history of FSGS, rather it should also be performed on individuals for whom drug-based therapies are not effective. In this case, kidney transplant is an effective alternative.

A Nomogram for Predicting Stroke Recurrence Among Young Adults.

Background and Purpose- This study aimed to develop and validate a nomogram for predicting the risk of stroke recurrence among young adults after ischemic stroke. Methods- Patients aged between 18 and 49 years with first-ever ischemic stroke were selected from the Nanjing Stroke Registry Program. A stepwise Cox proportional hazards regression model was employed to develop the best-fit nomogram. The discrimination and calibration in the training and validation cohorts were used to evaluate the nomogram. All patients were classified into low-, intermediate-, and high-risk groups based on the risk scores generated from the nomogram. Results- A total of 604 patients were enrolled in this study. Hypertension (hazard ratio [HR], 2.038 [95% CI, 1.504-3.942]; P=0.034), diabetes mellitus (HR, 3.224 [95% CI, 1.848-5.624]; P<0.001), smoking status (current smokers versus nonsmokers; HR, 2.491 [95% CI, 1.304-4.759]; P=0.006), and stroke cause (small-vessel occlusion versus large-artery atherosclerosis; HR, 0.325 [95% CI, 0.109-0.976]; P=0.045) were associated with recurrent stroke. Educational years (>12 versus 0-6; HR, 0.070 [95% CI, 0.015-0.319]; P=0.001) were inversely correlated with recurrent stroke. The nomogram was composed of these factors, and successfully stratified patients into low-, intermediate-, and high-risk groups (P<0.001). Conclusions- The nomogram composed of hypertension, diabetes mellitus, smoking status, stroke cause, and education years may predict the risk of stroke recurrence among young adults after ischemic stroke.

Symptomatic Intracranial Hemorrhage After Mechanical Thrombectomy in Chinese Ischemic Stroke Patients: The ASIAN Score.

BACKGROUND AND PURPOSE: Symptomatic intracranial hemorrhage (sICH), potentially associated with poor prognosis, is a major complication of endovascular thrombectomy (EVT) for ischemic stroke patients. We aimed to develop and validate a risk model for predicting sICH after EVT in Chinese patients due to large-artery occlusions in the anterior circulation. METHODS: The derivation cohort recruited patients with EVT from the Endovascular Treatment for Acute Anterior Circulation Ischemic Stroke Registry in China. sICH was diagnosed according to the Heidelberg Bleeding Classification within 24 hours of EVT. Stepwise logistic regression was performed to derive the predictive model. The discrimination and calibration of the risk model were assessed using the C index and the calibration plot. An additional cohort of 503 patients from 2 stroke centers was prospectively enrolled to validate the new model. RESULTS: We enrolled 629 patients who underwent EVT as the derivation cohort, among whom 87 developed sICH (13.8%). In the multivariate adjustment, Alberta Stroke Program Early CT Score (odds ratio [OR], 0.85; P=0.005), baseline glucose (OR, 1.13; P=0.001), poor collateral circulation (OR, 3.06; P=0.001), passes with retriever (OR, 1.52; P=0.001), and onset-to-groin puncture time (OR, 1.79; P=0.024) were independent factors of sICH and were incorporated as the Alberta Stroke Program Early CT Score, Baseline Glucose, Poor Collateral Circulation, Passes With Retriever, and Onset-to-Groin Puncture Time (ASIAN) score. The ASIAN score demonstrated good discrimination in the derivation cohort (C index, 0.771 [95% CI, 0.716-0.826]), as well as the validation cohort (C index, 0.758 [95% CI, 0.691-0.825]). CONCLUSIONS: The ASIAN score reliably predicts the risk of sICH in Chinese ischemic stroke patients treated by EVT.

Apolipoprotein B and renal function: across-sectional study from the China health and nutrition survey.

BACKGROUND: Chronic kidney disease (CKD) is a worldwide public health problem characterized by changes in kidney structure and function, usually leading to a loss of kidney function. The identification of risk factors and management of patients with early-stage CKD may slow or prevent the progression to end-stage renal disease. METHODS: This study used the population-based cohort database from the China Health and Nutrition Survey (CHNS). Data from 11,978 patients were collected from the 2009 to 2011 wave of the CHNS. After removing patients with missing data, we finally included 8322 participants. A cross-sectional design was used to assess the association between Apolipoprotein B (Apo-B) levels and CKD. We used overlapping covariates to develop 5 models to evaluate the odds ratios. RESULTS: Among the study participants, patients with estimated glomerular filtration rates (eGFR) < 60 ml/min/1.73m2were more likely to have increased Apo-B levels (> 1.2 mmol/L, 19.41%), likely to be elderly (> 65 years, 61.76%), likely to be female (61.21%), and likely to be less educated (< 6 years and > 6 & ≤12 years, 32.07 and 52.44%, respectively).The significant association between Apo-B and CKD defined by eGFR even after adjusting for confounders including demographic characteristics, nutritional status, comorbidities, biochemical indicators, and lifestyle factors. In addition, stratified analyses showed that young and middle age (< 65 years), being overweight (body mass index [BMI] > 25 kg/m2), and hyperuricemia were associated with higher risks of CKD stages. CONCLUSIONS: The results of this Chinese population-based study revealed a strong positive correlation between Apo-B and CKD stages. The current findings were obtained from an epidemiologic study; therefore, these data cannot directly address the mechanisms of disease progression. The underlying mechanisms require analysis in future independent validation and prospective cohort studies.