After early mTICI 2b, stop or continue? Insights from the PERSIST Registry.

OBJECTIVES: A higher reperfusion grade after endovascular thrombectomy (EVT) is associated with a good prognosis. However, the effect of the number of retrievals has not yet been investigated in vertebrobasilar occlusion (VBAO). Therefore, the aim of this study was to investigate whether to continue retrieval after early modified thrombolysis in cerebral infarction (mTICI) 2b to achieve a better reperfusion grade. METHODS: We retrospectively analyzed the data of patients who underwent EVT caused by VBAO in a multicenter registry dataset. Patients who underwent successful reperfusion were included (mTICI 2b/3). Regression models were used to analyze the correlation of different reperfusion grades stratified by the number of retrieval attempts with clinical prognosis and hemorrhage transition. RESULTS: We included 432 patients: 34.5% (n = 149) had a final mTICI score of 2b and 65.5% (n = 283) had a final mTICI score of 3. Patients who obtained a mTICI of 3 after the first pass had significantly increased odds of having a good prognosis. As the number of passes increases, the chances of obtaining a good prognosis decreases. After three or more passes, the odds of achieving functional independence and favorable outcomes were comparable to those of the first mTICI 2b, regardless of the 90-day (OR 1.132 95% CI 0.367-3.487 p = 0.829; OR 1.070 95% CI 0.375-3.047 p = 0.900) or 1-year follow-up (OR 1.217 95% CI 0.407-3.637 p = 0.725; OR 1.068 95% CI 0.359-3.173 p = 0.906). INTERPRETATION: Within two retrieval attempts, mTICI 3 was better than the first retrieval to mTICI 2b. After early mTICI 2b, each retrieval should be undertaken with caution to pursue a higher reperfusion grade.

Aberrant cerebral blood flow and functional connectivity in patients with vestibular migraine: a resting-state ASL and fMRI study.

BACKGROUND: Prior neuroimaging studies on vestibular migraine (VM) have extensively certified the functional and structural alterations in multiple brain regions and networks. However, few studies have assessed the cerebral blood flow (CBF) in VM patients using arterial spin labeling (ASL). The present study aimed to investigate CBF and functional connectivity (FC) alterations in VM patients during interictal periods. METHODS: We evaluated 52 VM patients and 46 healthy controls (HC) who received resting-state pseudo-continuous ASL and functional magnetic resonance imaging (fMRI) scanning. Comparisons of voxel-based CBF and seed-based FC were performed between the two groups. Brain regions showed significant group differences in CBF analyses were chosen as seeds in FC analyses. Additionally, the associations between abnormal imaging results and clinical features were explored. RESULTS: Compared with HC, VM patients showed higher normalized CBF in the right precentral gyrus (PreCG), left postcentral gyrus (PostCG), left superior frontal gyrus and bilateral insular (p < 0.05, FDR corrected). Furthermore, VM patients exhibited increased FC between the right PreCG and areas of the left PostCG, left cuneus and right lingual gyrus (p < 0.05, FDR corrected). In addition, we observed decreased FC between the left insular and regions of the left thalamus and right anterior cingulate cortex, as well as increased FC between the left insular and right fusiform gyrus in VM patients (p < 0.05, FDR corrected). Moreover, these variations in brain perfusion and FC were significantly correlated with multiple clinical features including frequency of migraine symptoms, frequency of vestibular symptoms and disease duration of VM (all p < 0.05). CONCLUSIONS: Patients with VM during interictal period showed hyperperfusion and abnormal resting-state FC in brain regions potentially contributed to disrupted multi-sensory and autonomic processing, as well as impaired ocular motor control, pain modulation and emotional regulation. Our study provided novel insights into the complex neuropathology of VM from a CBF perspective.

Temporal progression of functional independence after mechanical thrombectomy in acute vertebrobasilar artery occlusions.

BACKGROUND: Neurological recovery after endovascular treatment (EVT) for large vessel occlusion stroke often has diverse timelines. Understanding the temporal progression of functional independence after EVT, especially delayed functional independence (DFI) and highly delayed functional independence (HDFI), in patients who do not improve early is essential for prognostication and rehabilitation. We aimed to analyze the prevalence and predictors of DFI and HDFI after EVT in acute vertebrobasilar artery occlusions (VBAO). METHODS: Patients with VBAO who received EVT in China were retrospectively enrolled. Early functional independence (EFI) was defined as a modified Rankin Scale (mRS) score of 0-2 at discharge. The incidence and predictors of DFI (mRS score 0-2 at 90 days in non-EFI patients) and HDFI (mRS score 0-2 at 1 year in non-DFI patients) were analyzed. RESULTS: 2422 patients met the study criteria. EFI was observed in 20% (483) of patients. Among non-EFI patients, DFI was observed in 21% (395/1880). HDFI was observed in 13% (191/1439) of non-DFI patients. Younger age (P=0.006), lower pre-EVT National Institutes of Health Stroke Scale (NIHSS) score (P<0.001), higher posterior circulation-Alberta Stroke Program Early CT Score (PC-ASPECTS) (P=0.012), and absence of symptomatic intracranial hemorrhage (sICH) (P<0.001) were predictors of DFI. Predictors of HDFI were younger age (P<0.001) and lower pre-EVT NIHSS score (P<0.001). CONCLUSION: A considerable proportion of patients have DFI and HDFI. The independent predictors of DFI were younger age, lower pre-EVT NIHSS score, higher PC-ASPECTS, and absence of sICH. Predictors of HDFI included younger age and lower pre-EVT NIHSS score.

General anesthesia vs. non-general anesthesia for vertebrobasilar stroke endovascular therapy.

Background: The optimal type of anesthesia for acute vertebrobasilar artery occlusion (VBAO) remains controversial. We aimed to assess the influence of anesthetic management on the outcomes in VBAO patients received endovascular treatment (EVT). Methods: Patients underwent EVT for acute VBAO at 21 stroke centers in China were retrospectively enrolled and compared between the general anesthesia (GA) group and non-GA group. The primary outcome was the favorable outcome, defined as a modified Rankin Scale (mRS) score 0-3 at 90 days. Secondary outcomes included functional independence (90-day mRS score 0-2), and the rate of successful reperfusion. The safety outcomes included all-cause mortality at 90 days, the occurrence of any procedural complication, and the rate of symptomatic intracranial hemorrhage (sICH). In addition, we performed analyses of the outcomes in subgroups that were defined by Glasgow Coma Scale (GCS) score (≤8 or >8). Results: In the propensity score matched cohort, there were no difference in the primary outcome, secondary outcomes and safety outcomes between the two groups. Among patients with a GCS score of 8 or less, the proportion of successful reperfusion was significantly higher in the GA group than the non-GA group (aOR, 3.57, 95% CI 1.06-12.50, p = 0.04). In the inverse probability of treatment weighting-propensity score-adjusted cohort, similar results were found. Conclusions: Patients placed under GA during EVT for VBAO appear to be as effective and safe as non-GA. Furthermore, GA might yield better successful reperfusion for worse presenting GCS score (≤8). Registration: URL: http://www.chictr.org.cn/; Unique identifier: ChiCTR2000033211.

Effects of admission systemic inflammatory indicators on clinical outcomes in patients with vertebrobasilar artery occlusion: insight from the PERSIST registry.

BACKGROUND: Few studies have focused on the effect of systemic inflammation in vertebrobasilar artery occlusion (VBAO). The aim of this study was to investigate the relationship between inflammatory indicators and the prognosis of VBAO patients receiving endovascular treatment (EVT). METHOD: Patients with VBAO who were treated with EVT within 24 hours of the estimated occlusion time were included in this study. Multivariate logistic regression and elastic net regularization were performed to analyze the effects of inflammatory indicators on the prognosis of patients with VBAO. The primary outcome was unfavorable outcome (a modified Rankin Scale score of 4-6) at 90 days. Secondary outcomes included symptomatic intracranial hemorrhage, in-hospital mortality, 90 day mortality, 1 year unfavorable outcome, and mortality. RESULTS: 560 patients were included in the study. Multivariate analysis showed that white blood cells (W), neutrophils (N), neutrophil to lymphocyte ratio (NLR), platelet to neutrophil ratio, platelet to white blood cell ratio, and NLR to platelet ratio were associated with the primary outcome. Elastic net regularization indicated that W, N, and NLR were the major inflammatory predictors of unfavorable outcome at 90 days. For long term prognosis, we found that the inflammatory indicators that predicted 1 year outcomes were consistent with those that predicted 90 day outcomes. CONCLUSION: Inflammatory indicators, especially W, N, and NLR, were associated with moderate and long term prognosis of patients with VBAO treated with EVT.

First-pass effect in patients with acute vertebrobasilar artery occlusion undergoing thrombectomy: insights from the PERSIST registry.

Background: Achieving rapid and complete vascular recanalization in patients with acute large vessel occlusion can significantly improve patients' prognosis. Objective: We aimed to investigate the potential contribution of the first-pass effect (FPE) to the clinical outcome of patients with acute vertebrobasilar artery occlusion (VBAO). Methods: We retrospectively analyzed the data of patients who underwent endovascular thrombectomy (EVT) caused by VBAO in a multicentered retrospective registry dataset. FPE was defined as successful recanalization [modified thrombolysis in cerebral infarction (mTICI) 2b/3 as modified FPE (mFPE); mTICI 3 as true FPE (tFPE)] after one pass of the device without rescue therapy. The baseline characteristics and procedural and clinical outcomes were analyzed. Multivariate analysis was used to explore the predictors of FPE and the relationship between FPE and 90-day prognosis. Results: A total of 508 patients (age, 63.7 ± 13.1 years, male, 71.6%) were finally included, 29.9% (152/508) of whom achieved mFPE, and 21.1% (107/508) of whom achieved tFPE. FPE was significantly associated with improved clinical outcomes, regardless of mFPE [odds ratio (OR): 0.601, 95% confidence interval (CI): 0.370-0.977, p = 0.040] and tFPE (OR: 0.547, 95% CI: 0.318-0.940, p = 0.029). The use of contact aspiration, favorable collateral status, cardioembolic etiology, and basilar artery occlusion were statistically significant predictors of mFPE and tFPE, whereas hypertension was a negative predictor. Intravenous (IV) recombinant tissue plasminogen activator (rt-PA) prior to EVT was a positive predictor of mFPE but not of tFPE. Conclusion: FPE was associated with significantly favorable outcomes in EVT patients with VBAO. The predictors of FPE include infarct etiology, the site of occlusion, collateral status, EVT strategies, and IV rt-PA bridging strategies. Trial registration number: URL: http://www.chictr.org.cn/; Unique identifier: ChiCTR2000033211.

The safety and effectiveness of endovascular treatment for patients with vertebrobasilar artery occlusions: according to the BEST and BASICS criteria.

Background: Whether endovascular treatment (EVT) is safe and effective for vertebrobasilar artery occlusion (VBAO) is yet incompletely understood. Two RCTs, the endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST) trail and the Basilar Artery International Cooperation Study (BASICS), concentrating on this field were recently reported. Objective: We use real-world registry data of VBAO to compare the outcome of EVT inside and outside the inclusion and exclusion criteria of the BEST and BASICS study to testify the feasibility of the selection paradigms of VBAO in these trials. Methods: Consecutive patients with VBAO receiving EVT involving 21 stroke centers were retrospectively included. The safety outcomes [3-month mortality, symptomatic intracranial hemorrhage (sICH), and effectiveness outcomes (the proportion of 3-month functional independence (mRS of 0-2) and favorable outcome (mRS of 0-3)] were compared between VBAO patients who meet or failed to meet the BEST/BASICS selection criteria for EVT. Results: Our study cohort consisted of 577 VBAO patients who underwent EVT. Of them, 446 patients had pc-ASPECTS ≧8. Successful reperfusion (mTICI 2b or 3) was achieved in 85.4% (n = 493). There were 418 patients fulfilling the BEST criterion for EVT and 194 fulfilling the BASICS criterion. Regression analysis indicated that adherence to BEST or BASICS criterion for EVT was not independently related to most of the safety and effectiveness outcome except that adherence to BEST was significantly associated with the 3-month favorable outcome (ORBEST: 1.742, 95% CI: 1.087-2.790). However, when we put pc-ASPECTS into both criteria with a cut-off value of 8, meeting both BEST criterion plus pc-ASPECTS and BASICS criterion plus pc-ASPECTS was independently related to 3-month functional independence (ORBEST: 1.687, 95% CI: 1.077-2.644; ORBASIC: 1.653, 95% CI: 1.038-2.631) and favorable outcome (ORBEST: 2.280, 95% CI: 1.484-3.502; ORBASIC: 2.153, 95% CI: 1.372-3.378). Conclusion: Our study indicated that, based on real-world data of EVT, adherence to BEST or BASICS criterion for EVT was not independently associated with the safety and effectiveness outcome except that adherence to BEST was significantly related to the 3-month favorable outcome. However, the BEST or BASICS selection criterion and pc-ASPECTS ≧8 might be better paradigms for EVT patient selection.

Early blood pressure changes during systemic thrombolysis and its association with unexplained early neurological deterioration in small subcortical infarct.

Early neurological deterioration (END), observed in the acute phase of small subcortical infarct treated with intravenous thrombolysis (IVT), is not uncommon in these patients. However, in over half of the END cases, the exact cause is yet incompletely understood, which is so-called unexplained END (unEND). Our aim was to investigate the association of early blood pressure (BP) changes with unEND in patients with small subcortical infarct in the perforator territory of middle cerebral artery treated with IVT. Consecutive patients with acute small subcortical infarct treated with IVT were enrolled in this study. unEND was defined as≧2-point increase of NIHSS from baseline to 24 hours, without straightforward causes. BP excursions and BP variability were calculated and compared between patients with unNED and those without. A total of 168 patients with acute small subcortical infarct were included. Of them, there were 29 patients with unEND and 139 without END. During the first 24 hours following IVT, 66 (39.29%) patients had at least one BP excursion. Logistic regression analyses indicated that BP excursion presence (OR = 3.185, 95% CI: 1.238-8.198), SBP excursion presence (OR = 3.535, 95% CI: 1.366-9.143), and number of SBP excursion (OR = 1.466, 95% CI: 1.090-1.973) were independently associated with unEND. Although SBPSD (P < .001) and SBPCV (P < .001) were higher in patients with unEND than those without END, none of the parameters of BP variability predicted unEND in multivariate analyses. BP excursions above guideline thresholds during the first 24 hours following IVT for small subcortical infarct are common and are independently associated with unEND.

Clinical characteristics of cognitive impairment and its related risk factors in post-stroke epilepsy

Objective: Post-stroke epilepsy (PSE) patients are prone to cognitive impairment (CI) due to multiple factors. This study aimed to assess clinical characteristics of CI and its related risk factors in newly diagnosed Chinese Han adult epilepsy patients with ischaemic stroke. Methods: Data were collected on PSE patients hospitalized in the neurology ward of the Affiliated Hospital of Yangzhou University, from January 2016 to May 2019. Newly diagnosed PSE patients were followed for six months; their cognitive functions were then assessed according to the Chinese Beijing version of the Montreal Scale (MoCA) and patients were divided into a PSE+CI group (MoCA scale score <26) (n=81) or PSE-CI group (MoCA scale score ≥26) (n=36). Data collection tools also included the Chinese versions of the Zheng Self-assessment Anxiety Scale, the Zheng Self-assessment Depression Scale, the Barthel index and the National Hospital Seizure Severity Scale. We compared the basic clinical characteristics between the two groups of patients and investigated the factors of CI in PSE patients. Results: In total, CI was present in 81 (69%) and absent in 36 (31%) PSE patients. MoCA total score in the PSE+CI group was 20.85±4.13 and 27.53±1.34 in the PSECI group. The Bonferroni corrected significance level was 0.0013. Scores for multiple cognitive domains (visuospatial/executive skills, naming, attention, language and delayed recall) were lower in the PSE+CI group than the PSE-CI group. Moreover, the PSE+CI group had a higher incidence of depression and anxiety. Univariate analysis showed that diabetes (p= 0.000) and the number of antiepileptic drugs (AEDs) (p= 0.001) were associated with CI in PSE. Binary logistic regression analysis showed that diabetes (odds ratio [OR]: 5.242, 95% confidence interval [CI]: 1.680-16.363, p= 0.004), high homocysteine levels (OR: 1.103, 95% CI: 1.008-1.207, p= 0.033) and the number of AEDs (OR: 3.354, 95% CI: 1.225-9.180, p= 0.019) were associated with CI in PSE. Significance: Diabetes, high homocysteine levels and a higher number of AEDs may be risk factors for CI in PSE.

Optimisation of a Mouse Model of Cerebral Ischemia-Reperfusion to Address Issues of Survival and Model Reproducibility and Consistency.

Middle cerebral artery occlusion (MCAO) induced brain ischemia-reperfusion model in Mice is essential for understanding the pathology of stroke and investigating potential treatments, in which a variety of methods may be employed to block the middle cerebral artery (MCA), the most common being through the insertion of a monofilament; however, in vivo ischemia-reperfusion models are associated, particularly in mice, with high variability in lesion volume and high mortality. We aimed to optimise a mouse model of cerebral ischemia-reperfusion, addressing issues of mouse survival, model reproducibility, and consistency. The model was optimised in two ways: first, insert the monofilament directly through the internal carotid artery rather than through the external or common carotid artery, and second, by extending the length of the silicone coating on the monofilament, the length of the silicone coating enables embolization of the beginning of the middle cerebral artery, as well as the anterior cerebral artery and part of the posterior communicating artery. Results: We assessed various parameters, including blood flow changes in the middle cerebral artery, stability of the infarct area, correlation between infarct volume percentages and neurological deficit scores, mortality, weight changes, and wellbeing. We found that optimisation of the surgical procedure may improve mouse wellbeing and reduce mortality, through reduced weight loss and decrease the variability. In conclusion, we suggest that the optimisation of the model is superior for the study of both short and long-term outcomes of ischemic stroke. These results have considerable implications on stroke model selection for researchers.

The effect of metabolic syndrome and/or hyperglycemia on outcomes of acute ischemic stroke patients treated with intravenous thrombolysis.

BACKGROUNDS AND OBJECTIVES: The impact of metabolic syndrome (MetS)/hyperglycemia on the clinical outcomes of ischemic stroke treated with intravenous thrombolysis (IVT) remains controversial. This study aimed to determine the risks conferred by MetS and hyperglycemia to clinical outcomes in acute ischemic stroke patients treated with IVT. METHOD: Three hundred forty-three ischemic stroke patients treated with IVT were prospective recruited and stratified into four groups: neither, MetS only, hyperglycemia only, or both. The primary outcome was the 3-month poor functional outcome (PFO) which was defined as a 3-month modified Rankin Score (mRS) score ≧3. The secondary outcome included the hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) after IVT. RESULTS: MetS was recognized in 197 (57.43%) patients. During the first 24 h after IVT, 44 (12.83%) patients had HT, of which 17 had sICH. Three-month PFO was found in 98 (28.57%) patients. After adjustment for potential confounders, MetS (odds ratio (OR) = 3.140, 95% confidence interval (CI) = 1.724-5.718) was independently associated with PFO. However, neither MetS nor its components were associated with 24-h HT or sICH. In the further subgroup analysis, we used the "neither" group as reference and found that the presence of both MetS and hyperglycemia (OR = 3.192, 95% CI = 1.338-7.615) and the presence of hyperglycemia only (OR = 2.097, 95% CI = 1.052-4.179) were significantly related to the 3-month PFO. CONCLUSION: MetS is an independent risk factor on 3-month PFO in acute ischemic stroke patients treated with IVT. Compared with "neither," hyperglycemia only or concurrent with MetS was associated with an elevated risk of PFO after receiving IVT.

Incidental Unruptured Intracranial Aneurysms Do Not Impact Outcome in Patients With Acute Cerebral Infarction.

Background: This study was to examine the patients with acute cerebral infarction (ACI) treated at a single center over 9 years and who underwent Unruptured intracranial aneurysm (UIA) screening by three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA), and to explore the factors associated with outcomes. Methods: The outcome was the modified Rankin scale (mRS) score at 90 days after stroke onset. The outcome was classified into a good outcome (mRS score of 0-2 points) and poor outcome (mRS score of 3-6 points). Results: UIAs were found in 260 (6.5%) of 4,033 patients with ACI; 2,543 (63.1%) had a good outcome, and 1,490 (36.9%) had a poor outcome. There was no difference in outcomes between the two groups (P = 0.785). The multivariable analysis showed that age (OR = 1.009, 95%CI: 1.003-1.014, P = 0.003), diabetes (OR = 1.179, 95%CI: 1.035-1.342, P = 0.013), ischemic stroke history (OR = 1.451, 95%CI: 1.256-1.677, P < 0.001), and baseline NIHSS score (OR = 1.034, 95%CI: 1.018-1.050, P < 0.001) were independently associated with the 90-day outcomes in patients with ACI. The presence of incidental UIA was not associated with outcomes after ACI. Conclusions: Age, diabetes, ischemic stroke history, and baseline NIHSS score were independently associated with the early outcomes of patients with ACI.

Restored microRNA-326-5p Inhibits Neuronal Apoptosis and Attenuates Mitochondrial Damage via Suppressing STAT3 in Cerebral Ischemia/Reperfusion Injury.

Studies have greatly explored the role of microRNAs (miRNAs) in cerebral ischemia/reperfusion injury (CI/RI). But the specific mechanism of miR-326-5p in CI/RI is still elusive. Hence, this study was to unmask the mechanism of miR-326-5p/signal transducer and activator of transcription-3 (STAT3) axis in CI/RI. Two models (oxygen and glucose deprivation [OGD] in primary rat cortical neurons and middle cerebral artery occlusion [MCAO] in Sprague-Dawley rats) were established to mimic CI/RI in vitro and in vivo, respectively. Loss- and gain-of function assays were performed with OGD-treated neurons and with MCAO rats. Afterward, viability, apoptosis, oxidative stress and mitochondrial membrane potential in OGD-treated neurons were tested, as well as pathological changes, apoptosis and mitochondrial membrane potential in brain tissues of MCAO rats. Mitofusin-2 (Mfn2), miR-326-5p and STAT3 expression in OGD-treated neurons and in brain tissues of MCAO rats were detected. Mfn2 and miR-326-5p were reduced, and STAT3 was elevated in OGD-treated neurons and brain tissues of MCAO rats. miR-326-5p targeted and negatively regulated STAT3 expression. Restoring miR-326-5p or reducing STAT3 reinforced viability, inhibited apoptosis and oxidative stress, increased mitochondrial membrane potential and increased Mfn2 expression in OGD-treated neurons. Up-regulating miR-326-5p or down-regulating STAT3 relieved pathological changes, inhibited apoptosis and elevated mitochondrial membrane potential and Mfn2 expression in brain tissues of rats with MCAO. This study elucidates that up-regulated miR-326-5p or down-regulated STAT3 protects against CI/RI by elevating Mfn2 expression.

Sustained expression of MCP-1 induced low wall shear stress loading in conjunction with turbulent flow on endothelial cells of intracranial aneurysm.

Shear stress was reported to regulate the expression of AC007362, but its underlying mechanisms remain to be explored. In this study, to isolate endothelial cells of blood vessels, unruptured and ruptured intracranial aneurysm (IA) tissues were collected from IA patients. Subsequently, quantitative real-time PCR (qRT-PCR), Western blot and luciferase assay were performed to investigate the relationships between AC007362, miRNAs-493 and monocyte chemoattractant protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs) exposed to shear stress. Reduced representation bisulphite sequencing (RRBS) was performed to assess the level of DNA methylation in AC007362 promoter. Accordingly, AC007362 and MCP-1 were significantly up-regulated while miR-493 was significantly down-regulated in HUVECs exposed to shear stress. AC007362 could suppress the miR-493 expression and elevate the MCP-1 expression, and miR-493 was shown to respectively target AC007362 and MCP-1. Moreover, shear stress in HUVECs led to the down-regulated DNA methyltransferase 1 (DNMT1), as well as the decreased DNA methylation level of AC007362 promoter. Similar results were also observed in ruptured IA tissues when compared with unruptured IA tissues. In conclusion, this study presented a deep insight into the operation of the regulatory network of AC007362, miR-493 and MCP-1 upon shear stress. Under shear stress, the expression of AC007362 was enhanced by the inhibited promoter DNA methylation, while the expression of MCP-1 was enhanced by sponging the expression of miR-493.

Correlation of sexual dysfunction with sex hormone and estrogen receptor gene polymorphism in Chinese Han women with epilepsy.

OBJECTIVE: Women with epilepsy (WWE) have a high risk of sexual dysfunction (SD). We aimed to investigate the incidence of SD, the correlation between SD, sex hormone and estrogen receptor (ER) gene polymorphism in Chinese Han WWE. METHODS: This cross-sectional study examined 112 married WWE in the Affiliated Hospital of Yangzhou University who were taking antiepileptic drugs (AEDs) for ≥1 year, and 120 healthy controls without epilepsy, all of Chinese Han nationality. The age, menstruation, fertility of all the subjects and disease details of WWE were recorded. The Chinese version of female sexual function index (FSFI) was used to investigate the sexual function of the subjects. The chemiluminescence method was used for the detection of sex hormones, while polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the ER gene polymorphism. The differences of the sexual function, sex hormone, ER genotype, and allele frequency were compared between the two groups. The correlation between SD, sex hormone and ER gene polymorphism was also analyzed. RESULTS: (1) A high rate (70.5%) of SD was detected in WWE. (2) The serum prolactin (PRL) level (P = 0.039) and the ratio of estradiol to progesterone (E2/P) (P＜0.001) in the WWE group were significantly higher than those in the control group. The allele frequencies of ERα-PvuII C (P = 0.001) and ERß-AluI A (P = 0.001) in the WWE group were significantly higher than those in the control group. (3) Binary logistic regression analysis showed that serum testosterone level [odds ratio (OR) = 0.412, 95 % confidence interval (CI): 0.201-0.842, P = 0.015], and PvuII CC genotype [odds ratio (OR) = 6.074, 95 % confidence interval (CI): 1.257-29.352, P = 0.025] were independently correlated with SD. CONCLUSION: The incidence of SD in Chinese Han WWE is high. High serum testosterone levels may exert a protective effect on sexual function. ERα-PvuII polymorphism is related to the susceptibility of SD, and PvuII CC genotype may be the risk genotype of SD.

Acute in-hospital blood pressure variability predicts early neurological deterioration in acute minor stroke or transient ischemic attack with steno-occlusive arterial disease.

It is generally known that acute minor stroke and transient ischemic attack (TIA) seem to be benign. However, their occurrence in patients with steno-occlusive arterial disease may result in early neurological deterioration (END). We aimed to elucidate the effect of blood pressure variability (BPV) on the development of END. Consecutive acute minor stroke and TIA patients within 24 hours of onset were prospectively recruited from the Affiliated Hospital of Yangzhou University between Aug 2015 and Feb 2019. END was defined as an NIHSS score increased ≥1 during the first 72 hours compared with the initial NIHSS score. During this period, the mean, maximum (max), the difference between the maximum and minimum (max-min), the SD, and coefficient of variation of BP (BPCV ) were calculated. Of the 160 total patients enrolled in the study (mean age, 68.01 ± 9.33 years; 50.6% female), 52 (32.5%) patients occurred END during the first 72h after admission. To express the BPV as a categorical variable, we classified the subjects into one of four groups, representing four quartiles of BPV. In the multivariable analyses, the lowest quartiles were considered as reference groups. The results showed that patients who fell in the fourth quartile (SBPmax-min :OR = 3.289, 95% CI 1.147-9.430; SBPSD :OR = 3.313, 95% CI 1.041-10.547; SBPCV :OR = 3.425, 95% CI 1.164-10.077; DBPSD :OR = 3.124, 95% CI 1.065-9.158) had a significantly higher risk of END after adjusting the variables (age, female, diabetes mellitus, atrial fibrillation, and CRP with P values <.1 in univariate analyses). Our study demonstrated that the acute in-hospital BPV was associated with the development of END in acute minor stroke and TIA with steno-occlusive arterial disease.

Pterostilbene reduces endothelial cell injury in vascular arterial walls by regulating the Nrf2-mediated AMPK/STAT3 pathway in an atherosclerosis rat model.

Endothelial cell injury in vascular arterial walls is a hallmark of atherosclerosis. Pterostilbene (Pts) has been shown to have an anti-oxidative and anti-apoptotic effect in numerous diseases via regulation of intracellular metabolism. The purpose of this study was to investigate the protective effect and possible mechanism of Pts against endothelial cell apoptosis in an atherosclerotic rat model. An atherosclerotic rat model was established using a high-fat, high glucose and high cholesterol diet. The effects of Pts on apoptosis and oxidative stress injury were measured using atherosclerotic lesion analysis, western blot analysis, hematoxylin and eosin straining, TUNEL assay and immunohistochemistry. In vivo results in an atherosclerosis rat model showed that Pts administration decreased the inflammatory response. Pts administration attenuated atherogenesis, reduced aortic plaque size, reduced macrophage infiltration, and suppressed oxidative stress and apoptosis of vascular arterial walls. In vitro assays using cultured human endothelial cells showed that Pts administration decreased hydrogen peroxide-induced cytotoxicity, oxidative stress injury and apoptosis via nuclear factor erythroid 2-related factor 2 (Nrf2) activation in endothelial cells. Additionally, Pts administration increased the expression level of Nrf2 and 5' adenosine monophosphate-activated protein kinase (AMPK), and the phosphorylation level of AMPK and decreased signal transducer and activator of transcription 3 (STAT3) expression in these cells. Furthermore, knockdown of Nrf2 prevented Pts-decrease oxidative stress injury and apoptosis. In conclusion, these data suggest that Pts can protect endothelial cells in the vascular arterial walls against atherosclerosis-induced injury through regulation of the Nrf2-mediated AMPK/STAT3 pathway.

Relationship between high-sensitivity C-reactive protein and early neurological deterioration in stroke patients with and without atrial fibrillation.

BACKGROUND AND PURPOSE: The association of high-sensitivity C-reactive protein (hsCRP) with early neurological deterioration (END) is unclear, especially in stroke patients with atrial fibrillation (AF). In this study, we aimed to assess the association of baseline hsCRP levels with END in acute ischemic stroke with and without AF. METHODS: Consecutive acute ischemic stroke patients prospectively recruited from the Affiliated Hospital of Yangzhou University were analyzed and divided into two groups: AF related stroke (AF-S) and non-AF related stroke (Non-AF-S) groups. Plasma hsCRP levels on admission were categorized into three risk groups: low (<1.0 mg/L), average (1-3 mg/L) and high (>3 mg/L). RESULTS: A total of 655 consecutive patients diagnosed acute ischemic stroke were prospectively registered from our department in 2015-2018, which included 168 AF-S and 487 Non-AF-S cases. After standard therapy, 62 AF-S and 155 Non-AF-S cases developed END within 72 h of hospitalization. In AF-S cases, statistical differences between END and Non-END patients were found in age, gender, baseline National Institute of Health Stroke Scale (NIHSS) score, fasting blood glucose, responsible artery occlusion, CHA2DS2-VASc score and hsCRP level (p < 0.05). When variates showing p ≤ 0.1 in univariate analysis were adjusted, logistics regression analysis revealed following indexes as independent risk factors for END in AF-S patients: female (OR = 2.396, 95%CI:1.062-5.405, P = 0.035), fasting blood glucose (OR = 1.192, 95%CI:1.026-1.385, P = 0.022), responsible artery occlusion (OR = 3.589, 95%CI 1.425-9.036, P = 0.007), and high risk hsCRP (OR = 2.780, 95%CI 1.067-7.240, P = 0.036). In the Non-AF group, any level of hsCRP was not independently related to END after adjustment for age, sex, diabetes mellitus, smoking, baseline NIHSS, lesion size and responsible artery occlusion. CONCLUSION: High hsCRP level was independently correlated with END in patients with AF-S.