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Objective To explore the predictive value of intraoperative flat CT scan for intracranial hemorrhage after mechanical thrombectomy in patients with acute anterior circulation large vessel occlusion (AAC-LVO). Methods A total of 106 patients with AAC-LVO who underwent mechanical thrombectomy at The Second Affiliated Hospital of Bengbu Medical University was conducted from March 2020 to June 2023. Intraoperative flat CT scan was performed among above patients to record CT values, high-density sign and mass effect. According to whether occurred intracranial hemorrhage after surgery, those patients were divided into intracranial hemorrhage group (n = 29) and non-intracranial hemorrhage group (n = 77). Univariate and multivariate stepwise Logistic regression analyses were used to screen the influencing factors of intracranial hemorrhage after mechanical thrombectomy. Receiver operating characteristic (ROC) curve was drawn to evaluate the predictive efficacy of intraoperative flat CT scan for postoperative intracranial hemorrhage. Results Logistic regression analysis showed that hypertension was a protective factor for patients with AAC - LVO who did not experience intracranial hemorrhage after mechanical thrombectomy (OR = 0.340, 95%CI: 0.123-0.941; P = 0.038). A high National Institutes of Health Stroke (NIHSS) score at admission (OR = 1.068, 95%CI: 1.010-1.129; P = 0.021), as well as intraoperative flat CT high-density sign (OR = 9.942, 95%CI: 2.631-37.567; P = 0.001), mass effect (OR = 23.564, 95%CI: 7.266-79.421; P = 0.000), and CT value ≥ 90 HU (OR = 9.714, 95%CI: 1.982-47.605; P = 0.005) were risk factors for postoperative intracranial hemorrhage. The ROC curve showed that the area under the curve (AUC) for intraoperative flat CT value ≥ 90 HU, mass effect and their combined prediction of postoperative intracranial hemorrhage were 0.82 (95%CI: 0.734-0.889, P = 0.000), 0.75 (95%CI: 0.661-0.833, P = 0.000) and 0.76 (95%CI: 0.668-0.838, P = 0.000), with sensitivity were 75.86%, 58.62% and 58.62%, and specificity were 88.31%, 92.21% and 93.51%. The predictive efficiency was highest for CT value ≥ 90 HU (t = 48.777, P = 0.000; t = 43.681, P = 0.000). Conclusions In patients with AAC-LVO undergoing mechanical thrombectomy, intraoperative flat CT high-density sign such as CT value ≥ 90 HU and mass effect can predict postoperative intracranial hemorrhage, and the predictive value of CT value ≥ 90 HU is relatively high. [ABSTRACT FROM AUTHOR]

Salvianolic acid B (SalB), among the most abundant bioactive polyphenolic compounds found in Salvia miltiorrhiza Bge., exerts therapeutic and protective effects against various diseases. Although some summaries of the activities of SalB exist, there is lack of a scientometric and in-depth review regarding disease therapy. In this review, scientometrics was employed to analyze the number of articles, publication trends, countries, institutions, keywords, and highly cited papers pertaining to SalB research. The scientometric findings showed that SalB exerts excellent protective effects on the heart, lungs, liver, bones, and brain, along with significant therapeutic effects against atherosclerosis (AS), Alzheimer's disease (AD), liver fibrosis, diabetes, heart/brain ischemia, and osteoporosis, by regulating signaling pathways and acting on specific molecular targets. Moreover, this review delves into in-depth insights and perspectives, such as the utilization of SalB in combination with other drugs, the validation of molecular mechanisms and targets, and the research and development of novel drug carriers and dosage forms. In conclusion, this review aimed to offer a comprehensive scientometric analysis and in-depth appraisal of SalB research, encompassing both present achievements and future prospects, thereby providing a valuable resource for the clinical application and therapeutic exploitation of SalB. [ABSTRACT FROM AUTHOR]

Hyperlipidemia is a risk factor for stroke, and worsens neurological outcome after stroke. Endothelial progenitor cells (EPCs), which become dysfunctional in cerebral ischemia, hold capacity to promote revascularization. We investigated the role of dyslipidemia in impairment of EPC-mediated angiogenesis in cerebral ischemic mice. The high fat diet (HFD)-fed mice following by ischemic stroke exhibited increased infarct volumes and neurological severity scores, and poorer angiogenesis. Bone marrow-EPCs treated with palmitic acid (PA) showed impaired functions and inhibited activity of AMP-activated protein kinase (AMPK). Notably, AMPK deficiency aggravated EPC dysfunction, further decreased mitochondrial membrane potential, and increased reactive oxygen species level in EPCs with PA treatment. Furthermore, the expression of fatty acid oxidation (FAO)-related genes was remarkably reduced, and carnitine palmitoyltransferase 1A (CPT1A) protein expression was downregulated in AMPK-deficient EPCs. AMPK deficiency aggravated neurological severity scores and angiogenesis in ischemic brain of HFD-fed mice, accompanied by suppressed protein level of CPT1A. EPC transplantation corrected impaired neurological severity scores and angiogenesis in AMPK-deficient mice. Our findings suggest that AMPK deficiency aggravates poor angiogenesis in ischemic brain by mediating FAO and oxidative stress thereby inducing EPC dysfunction in hyperlipidemic mice. [ABSTRACT FROM AUTHOR]

Background: Salidroside is the major bioactive and pharmacological active substance in Rhodiola rosea L. It has been reported to have neuroprotective effects on cerebral ischemia/reperfusion (I/R). However, whether salidroside can enhance neural regeneration after cerebral I/R is still unknown. This study investigated the effects of salidroside on the endogenous neural regeneration after cerebral I/R and the related mechanism. Methods: Focal cerebral I/R was induced in rats by transient middle cerebral artery occlusion/reperfusion (MCAO/R). The rats were intraperitoneally treated salidroside once daily for 7 consecutive days. Neurobehavioral assessments were performed at 3 days and 7 days after the injury. TTC staining was performed to assess cerebral infarct volume. To evaluate the survival of neurons, immunohistochemical staining of Neuronal Nuclei (NeuN) in the ischemic hemisphere were conducted. Also, immunofluorescence double or triple staining of the biomarkers of proliferating neural progenitor cells in Subventricular Zone (SVZ) and striatum of the ischemia hemisphere were performed to investigate the neurogenesis. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of neurotrophic factors (NTFs) brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Expression of Notch1 and its target molecular Hes1 were also analyzed by western-blotting and RT-PCR. Results: Salidroside treatment ameliorated I/R induced neurobehavioral impairment, and reduced infarct volume. Salidroside also restored NeuN positive cells loss after I/R injury. Cerebral I/R injury significantly increased the expression of 5-Bromo-2'-Deoxyuridine (BrdU) and doublecotin (DCX), elevated the number of BrdU/Nestin/DCX triple-labeled cells in SVZ, and BrdU/Nestin/glial fibrillary acidic protein (GFAP) triple-labeled cells in striatum. Salidroside treatment further promoted the proliferation of BrdU/DCX labeled neuroblasts and BrdU/Nestin/GFAP labeled reactive astrocytes. Furthermore, salidroside elevated the mRNA expression and protein concentration of BDNF and NGF in ischemia periphery area, as well. Mechanistically, salidroside elevated Notch1/Hes1 mRNA expression in SVZ. The protein levels of them were also increased after salidroside administration. Conclusions: Salidroside enhances the endogenous neural regeneration after cerebral I/R. The mechanism of the effect may involve the regulation of BDNF/NGF and Notch signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Early prediction of delayed cerebral ischemia (DCI) is critical to improving the prognosis of aneurysmal subarachnoid hemorrhage (aSAH). Machine learning (ML) algorithms can learn from intricate information unbiasedly and facilitate the early identification of clinical outcomes. This study aimed to construct and compare the ability of different ML models to predict DCI after aSAH. Then, we identified and analyzed the essential risk of DCI occurrence by preoperative clinical scores and postoperative laboratory test results. Methods: This was a multicenter, retrospective cohort study. A total of 1039 post-operation patients with aSAH were finally included from three hospitals in China. The training group contained 919 patients, and the test group comprised 120 patients. We used five popular machine-learning algorithms to construct the models. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, precision, and f1 score were used to evaluate and compare the five models. Finally, we performed a Shapley Additive exPlanations analysis for the model with the best performance and significance analysis for each feature. Results: A total of 239 patients with aSAH (23.003%) developed DCI after the operation. Our results showed that in the test cohort, Random Forest (RF) had an AUC of 0.79, which was better than other models. The five most important features for predicting DCI in the RF model were the admitted modified Rankin Scale, D-Dimer, intracranial parenchymal hematoma, neutrophil/lymphocyte ratio, and Fisher score. Interestingly, clamping or embolization for the aneurysm treatment was the fourth button-down risk factor in the ML model. Conclusions: In this multicenter study, we compared five ML methods, among which RF performed the best in DCI prediction. In addition, the essential risks were identified to help clinicians monitor the patients at high risk for DCI more precisely and facilitate timely intervention. [ABSTRACT FROM AUTHOR]

Background: Astragaloside IV has emerged as a pharmaceutical monomer with great medical applications and potential. Astragaloside IV has many effects such as improving myocardial ischemia, cerebral ischemia–reperfusion injury, anti‐inflammatory, analgesic, antiviral, promoting lymphocyte proliferation, and antitumor effects. However, there are few bibliometric studies on astragaloside IV. Objectives: We aim to visualize the hotspots and trends in astragaloside IV research through bibliometric analysis to further understand the future development of basic and clinical research. Methods The articles and reviews on astragaloside IV were screened from the Web of Science Core Collection, and knowledge maps were generated using CiteSpace software. Bibliometric analysis was performed on 971 articles published from 1998 to 2022. Results: The number of articles on astragaloside IV increased yearly. These publications came from 42 countries/regions, with China being the largest. The primary research institutions were Shanghai University of Traditional Chinese Medicine and Guangzhou University of Traditional Chinese Medicine. Journal of Ethnopharmacology was the most studied journal and co‐cited journal. A total of 473 authors were included, among which Hongxin Wang had the highest number of publications and Zhang Wd had the highest total citation frequency. After analysis, the most common keywords are astragaloside IV, expression, and oxidative stress. Cardiovascular disease, cerebral ischemia, cancer, and kidney disease are current and developing research fields. Conclusion: This study used bibliometrics and visualization methods to analyze the research hotspots and trends of astragaloside IV. Astragaloside IV on ischemia–reperfusion injury, cancer, and tumor may become the focus of future research. [ABSTRACT FROM AUTHOR]

BACKGROUND: Evidence on acute stroke management is continuously growing. Stroke units are often associated with better access to high-level evidence-based practices, but even there, recommendations can be inconsistently delivered to patients with stroke. Implementation interventions are strategies designed to improve the application of evidence-based care. OBJECTIVE: To provide a commentary on the Cochrane Review by Lynch et al. on the effects of implementation interventions on adherence to evidence-based recommendations by health professionals working in acute stroke units. METHODS: A systematic search was performed in CENTRAL, MEDLINE, Embase, and other databases. The search was also performed in grey literature databases, trial registries, systematic reviews and primary studies, as well as in the reference list of identified studies. RESULTS: The review included seven cluster-randomized trials (with 42,489 participants). Studies compared the implementation of strategies composed of different parts (multifaceted) to no intervention, or a multifaceted strategy vs another intervention. These strategies were aimed at changing and improving the delivery of care in the hospital. It included health professional participants, such as nurses, physicians and allied health professionals. The authors concluded that there was uncertainty whether implementation strategies compared with no intervention have any effect on patients receiving evidence-based care during their stroke unit admission. Implementation interventions compared to no intervention probably have little or no effect on the risk of patients dying or being disabled or dependent, and probably do not change patients' hospital length of stay. CONCLUSION: Due to the very low certainty of evidence, there is uncertainty whether a multifaceted implementation intervention, compared to no intervention, can improve adherence to evidence-based recommendations in acute stroke settings. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the effects of electroacupuncture (EA) on cognitive recovery and synaptic remodeling in a rat model of middle cerebral artery occlusion (MCAO) followed by reperfusion and explore the possible mechanism. Method: Focal cerebral ischemia was modeled in healthy adult Sprague-Dawley rats by MCAO. The MCAO rats were classified into four groups: sham, MCAO, MCAO + GB20 (receiving EA at GB20) and MCAO + NA (receiving EA at a "non-acupoint" location not corresponding to any traditional acupuncture point location about 10 mm above the iliac crest). Neurological deficit scores and behavior were assessed before and during the treatment. After intervention for 7 days, the hippocampus was dissected to analyze growth-associated protein (GAP)-43, synaptophysin (SYN) and postsynaptic density protein (PSD)-95 expression levels by Western blotting. Bioinformatic analysis and primary hippocampal neurons with calcium-voltage gated channel subunit alpha 1B (CACNA1B) gene overexpression were used to screen the target genes for EA against MCAO. Results: Significant amelioration of neurological deficits and learning/memory were found in MCAO + GB20 rats compared with MCAO or MCAO + NA rats. Protein levels of GAP-43, SYN and PSD-95 were significantly improved in MCAO + GB20–treated rats together with an increase in the number of synapses in the hippocampal CA1 region. CACNA1B appeared to be a target gene of EA in MCAO. There were increased mRNA levels of CACNA1B, calmodulin (CaM), Ca2+/calmodulin-dependent protein kinase type II (CaMKII) and cyclic adenosine monophosphate response element binding (CREB) and increased phosphorylation of CaM, CaMKII and CREB in the hippocampal region in MCAO + GB20 versus MCAO and MCAO + NA groups. CACNA1B overexpression modulated expression of the CaM–CaMKII–CREB axis. Conclusion: EA treatment at GB20 may ameliorate the negative effects of MCAO on cognitive function in rats by enhancing synaptic plasticity. EA treatment at GB20 may exert this neuroprotective effect by regulating the CACNA1B–CaM–CaMKII–CREB axis. [ABSTRACT FROM AUTHOR]

Astragalus membranaceus is a traditional Chinese medicine derived from the roots of Astragalus membranaceus (Fisch.) Bge., which has the same medicinal and edible uses in China. It is also widely used in daily food, and its pharmacological effects mainly include antioxidant effects, vascular softening effects, etc. Currently, it is increasingly widely used in the prevention of hypertension, cerebral ischemia, and stroke in China. Formononetin and its glucopyranoside (ononin) are both important components of Astragalus membranaceuss and may play important roles in the treatment of cardiovascular diseases (CVDs). This study conducted metabolic studies using formononectin and its glucopyranoside (ononin), including a combination of the in vitro metabolism of Formonetin using rat liver S9 and the in vivo metabolism of ononin administered orally to rats. Five metabolites (Sm2, 7, 9, 10, and 12) were obtained from the solution incubated with formononetin and rat hepatic S9 fraction using chromatographic methods. The structures of the five metabolites were elucidated as (Sm2)6,7,4′-trihydroxy-isoflavonoid; (Sm7)7,4′-dihydroxy-isoflavonoid; (Sm9)7,8,4′-trihydroxy-isoflavonoid; (Sm10)7,8,-dihydroxy-4′-methoxy-isoflavonoid; and (Sm12)6,7-dihydroxy-4′-methoxy- isoflavonoid on the basis of UV, NMR, and MS data. Totally, 14 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSn analysis, from which the formononetin was incubated with rat hepatic S9 fraction, and the main metabolic pathways were hydroxylation, demethylation, and glycosylation. Then, 21 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSn analysis from the urine samples from SD rats to which ononin was orally administered, and the main metabolic pathways were glucuronidation, hydroxylation, demethylation, and sulfonation. The main difference between the in vitro metabolism of formononetin and the in vivo metabolism of ononin is that ononin undergoes deglycemic transformation into Formonetin in the rat intestine, while Formonetin is absorbed into the bloodstream for metabolism, and the metabolic products also produce combined metabolites during in vivo metabolism. The six metabolites obtained from the aforementioned separation indicate the primary forms of formononetin metabolism, and due to their higher contents of similar isoflavone metabolites, they are considered the main active compounds that are responsible for pharmacological effects. To investigate the metabolites of the active ingredients of formononetin in the rat liver S9 system, network pharmacology was used to evaluate the cardiovascular disease (CVD) activities of the six primary metabolites that were structurally identified. Additionally, the macromolecular docking results of six main components and two core targets (HSP90AA1 and SRC) related to CVD showed that formononetin and its main metabolites, Sm10 and Sm12, may have roles in CVD treatment due to their strong binding activities with the HSP90AA1 receptor, while the Sm7 metabolite may have a role in CVD treatment due to its strong binding activity with the SRC receptor. [ABSTRACT FROM AUTHOR]

Salvianolate (Sal) is a medicinal composition that is widely used in China for the treatment of coronary heart disease and angina pectoris. The aim of the present study was to investigate the potential macrophage-mediated pro-angiogenic effects of Sal in vitro. In addition, another aim was to explore the effects of Sal in a rat model of transient middle cerebral artery occlusion (tMCAO) along with the potential mechanism by which it promotes angiogenesis. In this study, human umbilical vein endothelial cells (HUVECs) and Raw264.7 macrophages in vitro, and a rat tMCAO model in vivo were used to detect the pro-angiogenic effect and mechanism of Sal. The results of in vitro experiments showed that the viability, migration and tube formation of HUVECs were promoted by the supernatant of Sal-treated Raw264.7 macrophages (s-Sal) but not by Sal alone. s-Sal also increased the levels of phosphorylated (p-)VEGFR-2, p-AKT and p-p38 MAPK in HUVECs while Sal alone did not. In vivo, treatment with Sal significantly reduced the cerebral infarction volume and neurological deficit scores in the rat tMCAO model. Similar to the mechanism observed in the in vitro experiments, Sal treatment upregulated the protein expression of VEGF and VEGFR-2, in addition to the phosphorylation of VEGFR-2, AKT and p38, in the brain tissues of the tMCAO model rats. In summary, the results of the present study suggest that the mechanism of Sal-mediated angiogenesis is associated with stimulation of the VEGF/VEGFR-2 signaling pathway by macrophages. This suggests the potential of Sal as a therapeutic option for the treatment of acute cerebral ischemic injury, which may act via the promotion of angiogenesis. [ABSTRACT FROM AUTHOR]

Background: Stent placement can be an effective treatment for patients with symptomatic intracranial stenosis (sICAS) and hemodynamic impairment (HI). However, the association between lesion length and the risk of recurrent cerebral ischemia (RCI) after stenting remains controversial. Exploring this association can help predict patients at higher risk for RCI and develop individualized follow-up schedules. Method: In this study, we provided a post-hoc analysis of a prospective, multicenter registry study on stenting for sICAS with HI in China. Demographics, vascular risk factors, clinical variables, lesions, and procedure-specific variables were recorded. RCI includes ischemic stroke and transient ischemic attack (TIA), from month 1 after stenting to the end of the follow-up period. Smoothing curve fitting and segmented Cox regression analysis were used to analyze the threshold effect between lesion length and RCI in the overall group and subgroups of the stent type. Results: The non-linear relationship between lesion length and RCI was observed in the overall population and subgroups; however, the non-linear relationship differed by subgroup of stent type. In the balloon-expandable stent (BES) subgroup, the risk of RCI increased 2.17-fold and 3.17-fold for each 1-mm increase in the lesion length when the lesion length was <7.70mmand >9.00mm, respectively. In the self-expanding stent (SES) subgroup, the risk of RCI increased 1.83-fold for each 1-mm increase in the lesion length when the length was <9.00mm. Nevertheless, the risk of RCI did not increase with the length when the lesion length was >9.00mm. Conclusion: A non-linear relationship exists between lesion length and RCI after stenting for sICAS with HI. The lesion length increases the overall risk of RCI for BES and for SES when the length was <9.00mm, while no significant relationship was found when the length was >9.00mm for SES. [ABSTRACT FROM AUTHOR]

The effect of surgical clipping (SC) and endovascular coiling (EC) on the incidence of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) has always been a controversial topic. Hence, it is necessary to reanalyze the effects of the 2 surgical methods on DCI, which determines the choice of the most favorable method for patients who are suitable for both surgical modalities. A multicenter retrospective observational cohort study was performed to evaluate all consecutive patients with aSAH admitted to 5 medical centers in China between April 2019 and June 2021. Univariable and multivariable analyses were used to confirm risk factors of DCI after aSAH. A 1:1 propensity score matching model was generated in the EC and SC groups to reduce the influence of all confounding factors on DCI. A total of 412 patients were included, and 115 patients (27.9%) developed DCI. After propensity score matching for controlling demographic information, past medical history, admission clinical status, aneurysm characteristics, and inflammatory factors associated with DCI, 133 patients with SC and 133 patients with EC treatment were matched. The results of the matched cohorts indicate a significantly lower incidence of DCI when patients received EC than SC (31.9% vs. 20%; adjusted odds ratio, 1.87; 95% confidence interval, 1.08–3.29; P = 0.027). The study found that the patients who received SC treatment had a higher incidence of DCI than did those who received EC and suggested that ruptured intracerebral aneurysm is preferentially coiled rather than clipped if the aneurysm is suitable for both surgical modalities. [ABSTRACT FROM AUTHOR]

Stroke has become the most common cause of death among residents in China, among which ischemic stroke accounts for the vast majority reaching 70% to 80%. It is of great importance to actively investigate the protective mechanism of cerebral ischemia injury after IS (ischemic stroke). We constructed cerebral ischemia injury models in vivo MACO rat and in vitro (oxygen-glucose deprivation cell model) and set up different interference groups. RT-PCR (reverse transcription PCR) was conducted to detect the expression of lncRNA in neuronal cells, brain tissue, and plasma of different groups, and ELISA (enzyme-linked immunosorbent assay) and western blot were used to detect the expression of the protein in neuronal cells, brain tissue, and plasma of different groups. Cell activity was detected by the CCK-8 assay, while cell apoptosis was examined by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay. In the rats' neuronal cells and brain tissue, curcumin can inhibit the expression of lncRNA GAS5 (long noncoding RNA growth arrest-specific 5). In oxygen-glucose-deprived neuronal cells in vitro, curcumin and low-expressed lncRNA GAS5 can enhance cell activity and decline cell apoptosis, but the addition of curcumin and overexpressed lncRNA GAS5 can make this phenomenon disappear. In neuronal cells, plasma, and brain tissue, curcumin and the low-expressed lncRNA GAS5 can inhibit the expression of IL-1β (interleukin 1 beta), TNF-α (tumor necrosis factor alpha), IL-6 (interleukin 6), Sox2 (SRY-box transcription factor 2), Nanog, and Oct4 (octamer-binding transcription factor 4). However, overexpressed lncRNA GAS5 and curcumin made the inhibitory effect disappear. In conclusion, this study demonstrated that curcumin could inhibit the expression of lncRNA GAS5, thereby inhibiting the expression of inflammation-related factors IL-1β, TNF-α, and IL-6, and ultimately achieve the purpose of attenuating cerebral ischemic cell damage. However, curcumin and lncRNA GAS5 may not alleviate cerebral ischemic cell damage by affecting stem cell differentiation. [ABSTRACT FROM AUTHOR]

Buzhong Yiqi decoction (BZYQD) has been developed for preventing or reducing the recurrence of ischemic stroke for a long time in China. However, the mechanism of action of the BZYQD is not completely understood. Our research aims to determine whether the mechanism of action of BZYQD is by regulating gut microbiota using 16SR RNA and fecal microbiota transplantation. In a cerebral ischemia mouse model, the results showed that prophylactic administration of BZYQD could reduce brain infarct volume and improve neurological function and behavior. The prophylactic administration of BZYQD could regulate intestinal microbiota and increase the abundance of butyrate-producing Prevotellaceae_NK3B31_group and probiotic Akkermansia in mice 72 h after surgery. Transplanting BZYQD-administered bacterial flora into antibiotic-depleted mice could reproduce the therapeutic effects of BZYQD. Overall, our study provided molecular insights into the mechanism and impact of BZYQD in the prevention of cerebral ischemic damage and highlighted the potential of regulation of intestinal microbiota as a therapeutic approach for ischemic stroke. [ABSTRACT FROM AUTHOR]

Background. Epidemiological surveys show that a large number of cerebrovascular diseases occur in China every year, and among these cerebrovascular diseases, ischemic diseases are predominant. Ischemia leads to irreversible degenerative necrosis of a large number of brain neurons and severe neurological deficits. Aims. This study is aimed at exploring the mechanism of the major regulatory effect of hypoxia-inducible factor 1 (HIF-1) pathway on proangiogenesis and providing new ideas for the treatment of ischemic stroke. Materials and Methods. The rats were randomly divided into normal and ischemic control groups, and the ischemic control group was subjected to the middle cerebral artery occlusion (MCAO) cerebral ischemia model by the wire embolization method, and the rats were executed in batches at 6 h, 1 d, and 3 d after ischemia-reperfusion, and the brain tissue specimens were taken for examination to investigate the effect of hypoxia-inducible factor 1 (HIF-l) signaling pathway on acute ischemic stroke. Results. At 3 d, the number of VEGFR2 positive cells increased significantly, and there was a significant difference compared with the control group (P < 0.05). At 3 d, the number of HIF-1α-positive cells increased significantly, and there was a significant difference compared with the control group (P < 0.05). The number of Hes1+factor VIII positive cells in the ischemic cortex increased significantly on the 1st and 3rd day, and there was a significant difference compared with the control group (P < 0.05). The expression of Hes1 protein was significantly lower than the normal level after 6 h of ischemia, and the protein expression was significantly increased at 1 d and 3 d after ischemia (P < 0.05). Conclusion. By detecting the expression changes of Hesl+factor VII in the ischemic area, the results show that ischemia and hypoxia activate the HIF-1, making the HIF-l the main regulatory pathway in the process of angiogenesis after ischemia. [ABSTRACT FROM AUTHOR]

Background: Anxiety might be a potentially modifiable risk factor of cardiovascular diseases (CVDs). Evidence relating anxiety symptoms and generalized anxiety disorder (GAD) to CVDs from prospective cohort study was still lacking in China.Methods: Participants aged 30 to 79 years old from 10 areas across China were recruited during 2004-2008 and were followed up until 2017. 487,209 participants without CVDs at baseline remained for analyses. Anxiety symptoms (panic attacks and continuous anxiety) during the past 12 months were identified in a face-to-face interview. Participants with continuous anxiety were further assessed for GAD using Composite International Diagnostic Interview-Short Form. The primary outcomes were incident CVD, ischaemic heart disease (IHD), haemorrhagic stroke (HS), and ischaemic stroke (IS).Results: During 4.7 million person-years of follow-up, we documented 140,365 incident cases of CVD. For panic attacks, the multivariable-adjusted HRs (95 % CI) were 1.08 (1.04-1.13), 1.10 (1.02-1.19), 1.20 (1.05-1.38) and 1.20 (1.11-1.30) for CVD, IHD, HS and IS, respectively. Continuous anxiety was positively associated with incident CVD and IHD, and the corresponding HRs were 1.12 (1.04-1.20) and 1.21 (1.07-1.37).Limitations: Anxiety symptoms were examined according to self-reported questionnaires, which could constitute key study limitations.Conclusions: Among the Chinese adults, those with anxiety symptoms or GAD might be important at-risk population of CVD. [ABSTRACT FROM AUTHOR]

Background: Timely and accurate prediction of delayed cerebral ischemia is critical for improving the prognosis of patients with aneurysmal subarachnoid hemorrhage. Machine learning (ML) algorithms are increasingly regarded as having a higher prediction power than conventional logistic regression (LR). This study aims to construct LR and ML models and compare their prediction power on delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Methods: This was a multicenter, retrospective, observational cohort study that enrolled patients with aneurysmal subarachnoid hemorrhage from five hospitals in China. A total of 404 aSAH patients were prospectively enrolled. We randomly divided the patients into training (N = 303) and validation cohorts (N = 101) according to a ratio of 75–25%. One LR and six popular ML algorithms were used to construct models. The area under the receiver operating characteristic curve (AUC), accuracy, balanced accuracy, confusion matrix, sensitivity, specificity, calibration curve, and Hosmer–Lemeshow test were used to assess and compare the model performance. Finally, we calculated each feature of importance. Results: A total of 112 (27.7%) patients developed DCI. Our results showed that conventional LR with an AUC value of 0.824 (95%CI: 0.73–0.91) in the validation cohort outperformed k-nearest neighbor, decision tree, support vector machine, and extreme gradient boosting model with the AUCs of 0.792 (95%CI: 0.68–0.9, P = 0.46), 0.675 (95%CI: 0.56–0.79, P < 0.01), 0.677 (95%CI: 0.57–0.77, P < 0.01), and 0.78 (95%CI: 0.68–0.87, P = 0.50). However, random forest (RF) and artificial neural network model with the same AUC (0.858, 95%CI: 0.78–0.93, P = 0.26) were better than the LR. The accuracy and the balanced accuracy of the RF were 20.8% and 11% higher than the latter, and the RF also showed good calibration in the validation cohort (Hosmer-Lemeshow: P = 0.203). We found that the CT value of subarachnoid hemorrhage, WBC count, neutrophil count, CT value of cerebral edema, and monocyte count were the five most important features for DCI prediction in the RF model. We then developed an online prediction tool (https://dynamic-nomogram.shinyapps.io/DynNomapp-DCI/) based on important features to calculate DCI risk precisely. Conclusions: In this multicenter study, we found that several ML methods, particularly RF, outperformed conventional LR. Furthermore, an online prediction tool based on the RF model was developed to identify patients at high risk for DCI after SAH and facilitate timely interventions. Clinical Trial Registration: http://www.chictr.org.cn, Unique identifier: ChiCTR2100044448. [ABSTRACT FROM AUTHOR]

Buyang Huanwu decoction (BHD) is a well-known Chinese herbal prescription. It has been widely used in the clinical treatment of cerebral ischemia (CI) in China. However, the mechanism underlying the treatment of CI with BHD remains to be elucidated. In this study, we combined microbiomic and metabolomic strategies to explore the therapeutic effects of BHD on middle cerebral artery occlusion (MCAO) in rats. Our results showed that BHD could effectively improve neurological severity scores and alleviate neuronal damage in rats with MCAO. BHD could also reduce the level of peripheral proinflammatory cytokines and inhibit neuroinflammation. 16S rRNA sequencing showed that BHD could increase the relative abundances of the genera Lactobacillus , Faecalibacterium , Ruminococcaceae_UCG-002 , etc., while decreasing the relative abundances of the genera Escherichia-Shigella, Klebsiella, Streptococcus, Coprococcus_2 , Enterococcus , etc. Untargeted metabolomic analysis of hippocampal samples showed that 17 significantly differentially abundant metabolites and 9 enriched metabolic pathways were linked with BHD treatment. We also found that the regulatory effects of BHD on metabolites were correlated with the differentially abundant microbial taxa. The predicted function of the gut microbiota and the metabolic pathway enrichment results showed that purine metabolism, glutamatergic synapses, arginine and proline metabolism, and alanine, aspartic acid and glutamate metabolism were involved in the effects of BHD. These pathways may be related to pathological processes such as excitotoxicity, neuroinflammation, and energy metabolism disorder in CI. In summary, these findings suggest that regulation of hippocampal metabolism and of the composition and function of the gut microbiota may be important mechanisms underlying the effect of BHD in the treatment of CI. [ABSTRACT FROM AUTHOR]

Panax ginseng and Panax notoginseng, two well-known herbs with enormous medical value in Asian countries, have a long usage history in China for the therapy of some diseases, such as stroke. Ginsenoside Rb1 is one of most important active ingredients in Panax ginseng and Panax notoginseng. In the last two decades, more attention has focused on ginsenoside Rb1 as an antioxidative, anti-apoptotic and anti-inflammatory agent that can protect the nervous system. In the review, we summarize the neuroprotective roles of ginsenoside Rb1 and its potential mechanisms in central nervous system diseases (CNSDs), including neurodegenerative diseases, cerebral ischemia injury, depression and spinal cord injury. In conclusion, ginsenoside Rb1 has a potential neuroprotection due to its inhibition of oxidative stress, apoptosis, neuroinflammation and autophagy in CNSDs and may be a promising candidate agent for clinical therapy of CNSDs in the future. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical effect of cerebral vascular disease treated by transplantations of the short-segment radial artery (RA) using the internal maxillary artery (IMA) as the feeding artery. Methods and Results The clinical data of 5 cases with cerebral vascular disease treated by IMA-RA-cerebral artery bypass (IMAB) from August 2018 to April 2021 in the First Hospital of China Medical University were retrospectively analyzed. There were 3 cases of dissecting aneurysms [one case of right middle cerebral artery (MCA) M2 segment, one case of left MCA M1 segment, one case of right posterior cerebral artery (PCA) P2 segment], and 2 cases of vertebral basilar artery ischemia [one case of bilateral vertebral artery (VA) occlusion, one case of severe basilar artery (BA) stenosis]. Two patients underwent the IMA-RA-M2 bypass, and 3 patients underwent the IMA-RA-P2 bypass. Intraoperative indocyanine green angiography (ICGA) and Doppler ultrasonography confirmed patency of the RA in 4 cases and occluded RA in one case (the anastomosis of IMA-RA was opened, the intima of IMA was dissociated from the media, and RA was unobstructed after resuture). One patient developed basal ganglia infarction after the surgery. The RA blood flow was measured by ultrasound 123, 51, 77, 69 ml/min in 4 patients at one week after the surgery. One patient had a RA blood flow of 89 ml/min on 6 months after the surgery (69 ml/min on one week after the surgery), and one patient had a RA blood flow of 66 ml/min 26 months after the surgery (51 ml/min on one week after the surgery). One patient with dissociated M1 segment aneurysm with ischemic onset developed ischemic infarction in basal ganglia region after open aneurysm and bypass, and modified Rankin Scale (mRS) increased by one point on one week after surgery. mRS score of 3 patients decreased by one point and one patient had no change; after 8-40 months of follow-up, all patients recovered well, with mRS score of 0 in 2 cases, one in 2 cases, and 2 in one case. Conclusions The IMAB can provide moderate flow of blood supply to brain tissue, and the RA has good patency and stable flow during long-term follow-up. This operation can be used to treat patients with cerebral vascular disease of choosy and reduce the risk of cerebral ischemia effectively. [ABSTRACT FROM AUTHOR]

Background: Patients suffered aneurysmal subarachnoid hemorrhage (aSAH) usually develop poor survival and functional outcome. Evaluating aSAH patients at high risk of poor outcome is necessary for clinicians to make suitable therapeutical strategy. This study is conducted to develop prognostic model using XGBoost (extreme gradient boosting) algorithm in aSAH. Methods: A total of 351 aSAH patients admitted to West China hospital were identified. Patients were divided into training set and test set with ratio of 7:3 to testify the predictive value of XGBoost based prognostic model. Additionally, logistic regression model was also constructed and compared with XGBoost based model. Area under the receiver operating characteristic curve (AUC), sensitivity and specificity were calculated to evaluate the value of XGBoost and logistic regression. Results: There were 74 (21.1%) non-survivors and 148 (42.1%) patients with unfavorable functional outcome. Non-survivors had older age (p=0.025), lower Glasgow coma scale (GCS) (p< 0.001), higher World Federation of Neurosurgical Societies WFNS score (p< 0.001), mFisher score (p< 0.001). The incidence of intraventricular hemorrhage (IVH) (p=0.025) and delayed cerebral ischemia (DCI) (p< 0.001) was higher in non-survivors than survivors. The AUC of XGBoost model for predicting mortality and unfavorable functional outcome were 0.950 and 0.958, which were higher than 0.767 and 0.829 of logistic regression model. Conclusion: XGBoost based model is more precise than logistic regression model in predicting outcome of aSAH patients. Using XGBoost prognostic model is helpful for clinicians to identify high-risk aSAH patients and therefore strengthen medical care. [ABSTRACT FROM AUTHOR]

Daidzein is a plant isoflavonoid primarily isolated from Pueraria lobate Radix as the dry root of P. lobata (Wild.) Ohwi, have long been used as nutraceutical and medicinal herb in China. Despite the report that daidzein can prevent neuronal damage and improve outcome in experimental stroke, the mechanisms of this neuroprotective action have been not fully elucidated. The aim of this study was to determine whether the daidzein elicits beneficial actions in a stroke model, namely, cerebral ischemia/reperfusion (I/R) injury, and to reveal the underlying neuroprotective mechanisms associated with the regulation of Akt/mTOR/BDNF signal pathway. The results showed that I/R, daidzein treatment significantly improved neurological deficits, infarct volume, and brain edema at 20 and 30 mg/kg, respectively. Meanwhile, it was found out that the pretreatment with daidzein at 20 and 30 mg/kg evidently improved striatal dopamine and its metabolite levels. In addition, daidzein treatment reduced the cleaved Caspase-3 level but enhanced the phosphorylation of Akt, BAD and mTOR. Moreover, daidzein at 30 mg/kg treatment enhanced the expression of BDNF and CREB significantly. This protective effect of daidzein was ameliorated by inhibiting the PI3K/Akt/mTOR signaling pathway using LY294002. To sum up, our results demonstrated that daidzein could protect animals against ischemic damage through the regulation of the Akt/mTOR/BDNF channel, and the present study may facilitate the therapeutic research of stroke. [ABSTRACT FROM AUTHOR]

Flavonoid glycoside scutellarin (SCU) has been widely applied in the treatment of cerebral ischemic diseases in China. In this article, we conducted research on the working mechanisms of SCU in hypoxia reoxygenation (HR) injury of isolated cerebral basilar artery (BA) and erebral ischemia reperfusion (CIR) injury in rat models. In isolated rat BA rings, HR causes endothelial dysfunction (ED) and acetylcholine (ACh) induces endothelium-dependent vasodilation. The myography result showed that SCU (100 µM) was able to significantly improve the endothelium-dependent vasodilation induced by Ach. However, SCU did not affect the ACh-induced relaxation in normal BA. Further studies suggested that SCU (10–1000 µM) dose-dependently induced relaxation in isolated BA rings which were significantly blocked by the cGMP dependent protein kinase (PKG) inhibitor Rp-8-Br-cGMPs (PKGI-rp, 4 µM). Pre-incubation with SCU (500 µM) reversed the impairment of endothelium-dependent vasodilation induced by HR, but the reversing effect was blocked if PKGI-rp (4 µM) was added. The brain slice staining test in rats' model of middle cerebral artery occlusion (MCAO) induced CIR proved that the administration of SCU (45, 90 mg/kg, iv) significantly reduced the area of cerebral infarction. The Western blot assay result showed that SCU (45 mg/kg, iv) increased brain PKG activity and PKG protein level after CIR surgery. In conclusion, our findings suggested that SCU possesses the ability of protecting brain cells against CIR injury through vascular endothelium protection and PKG signal. [ABSTRACT FROM AUTHOR]

[Display omitted] Longxuetongluo Capsule (LTC) is wildly applied to treat ischemic stroke in clinical practice in China. However, the pharmacological mechanism of LTC on ischemic stroke is still unstated. Our research was designed to study the protective effect of LTC against cerebral ischemia–reperfusion (I/R) injury and reveal the underlying mechanism both in vivo and in vitro. PC12 cells treated with glucose deprivation/reperfusion (OGD/R) were used to simulate in vitro ischemia/reperfusion (I/R) injury. The cell viability, apoptosis rate, and protein expressions of PC12 cells were evaluated. In vivo validation of the protective effect of LTC was carried out by middle cerebral artery occlusion (MCAO)/reperfusion treatment, and the underlying mechanism of its anti-apoptosis ability was further revealed by immunohistochemistry staining and Western blotting. In the current study, we observed that LTC effectively inhibited oxygen-glucose deprivation/reperfusion (OGD/R) induced apoptosis of PC12 cells through suppressing the cleavage of poly ADP-ribose polymerase (PARP), caspase-3, and caspase-9. Further investigation revealed that OGD/R insult remarkably triggered the endoplasmic reticulum stress responses (ER stress) to induce PC12 cell apoptosis. LTC treatment alleviated OGD/R induced ER stress by inhibiting the activation of protein kinase RNA (PKR)-like ER kinase (PERK)/eukaryotic translation initiation factor 2 (eIF2α) and inositol requiring enzyme 1 (IRE1)/tumor necrosis factor receptor-associated factor 2 (TRAF2) pathways. Additionally, LTC also restrained the OGD/R-induced PC12 cell apoptosis by reversing the activated mitogen-activated protein kinase (MAPK) through IRE1/TRAF2 pathway. Animal studies demonstrated LTC significantly restricted the infarct region induced by middle cerebral artery occlusion (MCAO)/reperfusion, the activation of ER stress and apoptosis of neuronal cells had also been suppressed by LTC in the penumbra region. LTC protects the cerebral neuronal cell against ischemia/reperfusion injury through ER stress and MAPK-mediated mechanisms. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory infections have been associated with a transient increase in cardiovascular risk. However, whether such an association persists beyond 1 month and the potential modifying effect of cardiovascular risk factors on such an association are less well established.Methods: The China Kadoorie Biobank enrolled 512 726 participants aged 30-79 years from 10 areas across China during 2004-2008. By the end of 2017, a total of 5444 participants with new-onset ischaemic heart disease (IHD) and 4846 with ischaemic stroke (IS) who also had at least a record of hospitalization for pneumonia during follow-up were included. We used a self-controlled case-series method and calculated the age- and season-adjusted relative incidences (RIs) and 95% confidence intervals (CIs) for ischaemic cardiovascular disease (CVD) after pneumonia.Results: The risk of ischaemic CVD increased during days 1-3 after pneumonia hospitalization, with an RI (95% CI) of 4.24 (2.92-6.15) for IHD and 1.85 (1.02-3.35) for IS. The risk gradually reduced with longer duration since pneumonia hospitalization but remained elevated until days 92-365 for IHD (1.23, 1.12-1.35) and days 29-91 for IS (1.25, 1.05-1.48). Pre-existing cardiovascular risk factors amplified the associations between pneumonia and ischaemic CVD risks, such as chronic obstructive pulmonary disease for both IHD and IS, and diabetes and smoking for IHD (all Pinteraction < 0.05). Besides, the risk of ischaemic CVD was also higher among the participants aged ≥70 years (Pinteraction < 0.001 for IHD and 0.033 for IS).Conclusion: Among middle-aged and older Chinese adults, pneumonia hospitalization was associated with both short- and long-term increases in ischaemic CVD risk for ≤1 year. [ABSTRACT FROM AUTHOR]

Thymus quinquecostatus Celak., a member of thymus genus in Lamiaceae family, has been used as a folk medicine for relieving exterior syndrome and alleviating pain in China. The polyphenol-rich fraction (PRF) derived from Thymus quinquecostatus Celak. had been validated that it can protect cerebral ischemia-reperfusion injury (CIRI) by activating Keap1/Nrf2/HO-1 signaling pathway. Aim of this study : To explore effective components and their pharmacokinetic and pharmacodynamic characteristics as well as possible mechanisms of PRF in treating CIRI. Normal treated group (NTG) and tMCAO model treated group (MTG) rats were administrated PRF intragastrically. The prototype components and metabolites of PRF in plasma and brain were analyzed by the UPLC-Q-Exactive Orbitrap MSn method. Subsequently, the pharmacokinetics properties of indicative components were performed based on HPLC-QQQ-MS/MS. SOD and LDH activities were determined to study the pharmacodynamic (PD) properties of PRF. The PK-PD relationship of PRF was constructed. In addition, the effect of PRF on endogenous metabolites in plasma and brain was investigated using metabolomic method. Salvianic acid A, caffeic acid, rosmarinic acid, scutellarin, and apigenin-7- O -glucuronide were selected as indicative components based on metabolic analysis. The non-compartmental parameters were calculated for indicative components in plasma and brain of NTG and MTG rats. Furthermore, single-component and multi-component PK-PD modeling involved E max , I max PD models for effect indexes were fitted as well as ANN models were established, which indicated that these components can work together to regulate SOD and LDH activities in plasma and SOD activity in brain tissue to improve CIRI. Additionally, PRF may ameliorate CIRI by regulating the disorder of endogenous metabolites in lipid metabolism, amino acid metabolism, and purine metabolism pathways in vivo , among which lipid metabolism and purine metabolism are closely related to oxidative stress. The PK-PD properties of effect substances and mechanisms of PRF anti-CIRI were further elaborated. The findings provide a convincing foundation for the application of T. quinquecostatus Celak. in the maintenance of human health disorders. [Display omitted] • The prototype components and metabolites of PRF in plasma and brain were analyzed. • The ADMET properties of PRF were explored by pharmacokinetic study. • The single-component and multi-component integrated as well as ANN PK-PD modelings were established and clarified the effective components of PRF anti-CIRI. • PRF improved CIRI mainly by regulating the disorder of amino acid metabolism, lipid metabolism, and purine metabolism. [ABSTRACT FROM AUTHOR]

Background: Cerebral infarction and cerebral hemorrhage, also known as "stroke", is one of the leading cause of death. At present, there is no real specific medicine for stroke. Crinis Carbonisatus (named Xue-yu-tan in Chinese), produced from carbonized hair of healthy human, and has been widely applied to relieve pain and treat epilepsy, stroke and other diseases in China for thousands of years. Results: In this work, a new species of carbon dots derived from Crinis Carbonisatus (CrCi-CDs) were separated and identified. And the neuroprotective effect of carbon dots from CrCi were evaluated using the middle cerebral artery occlusion (MCAO) model. Neurological deficit score and infarction volume was assessed, evans blue content of ischemic hemispheres was measured, the concentrations of inflammatory factors, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) in the cortex were measured, and the levels of neurotransmitters in the brain were determined. Preconditioning of CrCi-CDs significantly reduced ischemic lesion volume and blood–brain-barrier (BBB) permeability, improved neurologic deficits, decreased the level of TNF-α and IL-6 in MCAO rats, inhibited excitatory neurotransmitters aspartate (Asp) and glutamate (Glu), and increased the level of 5-hydroxytryptamine (5-HT). The RNA-Sequencing results reveal that further potential mechanisms behind the activities may be related to the anti-inflammation effects and inhibition of neuroexcitatory toxicity. Conclusion: CrCi-CDs performs neuroprotective effect on cerebral ischemia and reperfusion injury, and the mechanisms may correlate with its anti-inflammatory action, which suggested that CrCi-CDs have potential value in clinical therapy on the acute apoplexy cases in combination with thrombolytic drugs. [ABSTRACT FROM AUTHOR]

Objective(s): Ginkgo biloba leaf extract (EGb-761) injection has been widely used as adjuvant therapy for cerebral stroke in China. However, its underlying pharmacological mechanism is not completely understood. The present study aimed to investigate whether the therapeutic effects of EGb-761 are exerted by modulating autophagy flux. Materials and Methods: Ischemic cerebral stroke was prepared in male Sprague-Dawley rats by middle cerebral artery occlusion (MCAO) followed by reperfusion. The MCAO/reperfusion rats were then treated with EGb-761 injection once daily for 7 days. Thereafter, the brain tissues in the ischemic penumbra were obtained to detect the key proteins in the autophagic/lysosomal pathway with Beclin1, LC3, (SQSTM1)/p62, ubiquitin, LAMP-1, cathepsin B, and cathepsin D antibodies by western blot and immunofluorescence. Meanwhile, the infarct volume, neurological deficits, and neuronal apoptosis were assessed to evaluate the therapeutic outcomes. Results: The results illustrated that EGb-761 treatment was not only able to promote the autophagic activities of Beclin1 and LC3-II in neurons, but also could enhance the autophagic clearance, as indicated by reinforced lysosomal activities of LAMP-1, cathepsin B, and cathepsin D, as well as alleviating autophagic accumulation of ubiquitin and insoluble p62 in the MCAO+EGb-761 group, compared with those in the MCAO+saline group. Meanwhile, cerebral ischemia-induced neurological deficits, infarct volume, and neuronal apoptosis were significantly attenuated by 7 days of EGb-761 therapy. Conclusion: Our data suggest that EGb-761 injection can elicit a neuroprotective efficacy against MCAO/reperfusion injury, and this neuroprotection may be exerted by enhancement of autophagy flux in neurons in the ischemic penumbra. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy and safety of low flow bypass in the treatment of chronic symptomatic middle cerebral artery occlusion (MCAO). Methods A total of 28 patients with chronic symptomatic MCAO who were treated in Tianjin Huanhu Hospital from January 2016 to December 2019 underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass, and the prognosis of neurological function was assessed by modified Rankin Scale (mRS). DSA or CTA were reexamined to evaluate the patency of the anastomotic site of the bridging vessels, and PWI was reexamined to evaluate improvement of cerebral perfusion. Results All 28 patients underwent STA-MCA bypass successfully, the success rate of operation was 100%, and the patency rate of bridge vessels was 100%. The postoperative neurological function was improved compared with that before operation, and the difference was statistically significant (mRS score 1.43 ± 0.57 vs. 2.14 ± 0.36; t = 6.301, P = 0.000). Twelve months after operation, the cerebral blood flow (CBF) and cerebral blood volume (CBV) of the affected side were significantly increased, and the mean transit time (MTT) and time to peak (TTP) were significantly decreased compared with those before operation. The mean postoperative follow-up was (39.41 ± 9.39) months. No new ischemic events occurred, and the bridge vessels were patchy. Conclusions Low flow bypass is safe and effective in the treatment of chronic symptomatic MCAO. [ABSTRACT FROM AUTHOR]

Background Bypass surgery for moyamoya disease (MMD) mainly used the middle cerebral artery (MCA) as the recipient artery. There is a high risk of ischemia in the blood supply area of the anterior cerebral artery (ACA) during the perioperative period and follow-up period. This study compared and analyzed the efficacy of superficial temporal artery (STA)-ACA and STA-MCA double barrel bypass and STA-MCA double barrel bypass in the treatment of MMD. Methods In total 41 hemispheres of 32 ACA territory ischemic MMD patients were treated from January 2017 to December 2020 in The First Hospital of China Medical University. Separately performed STA-ACA and STA-MCA double barrel bypass and encephalo-myosynangiosis (EMS; ACA group, 10 hemispheres of 10 patients) and STA-MCA double barrel bypass and EMS (MCA group, 31 hemispheres of 25 patients). Compared and analyzed STA blood flow [including cut flow (CF), blood flow and cut flow index (CFI)], bypass vascular patency, cerebral perfusion [including the relative value of mean transit time (MTT), time to peak (TTP), cerebral blood flow (CBF) and cerebral blood volume (CBV)], neurological prognosis [modified Rankin Scale (mRS)], and the cerebral ischemia and intracranial hemorrhage morbidity and mortality in perioperative period and follow-up period. Results Thirty-two patients successfully completed 41 hemisphere operations. Intraoperative STA CF value of ACA group was significantly lower than MCA group [24.00 (15.38, 53.00) ml/min vs. 47 (36, 70) ml/min; Z = -2.547, P = 0.011]. CFI of STA one week after operation of ACA group was significantly greater than MCA group [3.57 (1.66, 4.66) vs. 1.30 (0.75, 1.70); Z = -2.357, P = 0.018]. No statistical significance between 2 groups in STA blood flow one week after operation [82.00 (62.50, 103.00) ml/min vs. 75.00 (27.90, 104.50) ml/min; Z = -0.221, P = 0.825]. The ACA group anastomotic patency rate was 12/12 and the MCA group was 81.58% (31/38), the difference was not statistically significant (χ2 = 1.268, P = 0.260). Bilateral frontal ischemia was observed in one hemisphere operation (1/10) in ACA group at perioperative period. Frontal ischemia was observed in 4 hemisphere operations (12.90%) and hemorrhagic temporal occipital infarction was observed in one hemisphere operation (3.23%) in MCA group at perioperative period. There was no statistically significant difference in the morbidity between 2 groups (Fisher exact probability: P = 1.000). No cerebral ischemia, intracranial hemorrhage and death occurred in ACA group, and surgical side frontal ischemia was observed in one hemisphere operation one year after operation in MCA group. There was no statistically significant difference in the morbidity between 2 groups (Fisher exact probability: P = 1.000). ACA group improved in 6 hemisphere operations (6/10), no changed in 3 hemisphere operations (3/10), deteriorated in one hemisphere operation (1/10). MCA group improved in 10 hemisphere operations (32.26%), no changed in 17 hemisphere operations (54.84%), deteriorated in 4 hemisphere operations (12.90%). There was no statistically significant difference between 2 groups (Z = -1.355, P = 0.223). Conclusions The STA-ACA and STA-MCA double barrel bypass in the treatment of ACA territory ischemic MMD patients can obtain good anastomotic patency rate and satisfactory long-term efficacy. Compared with the STA-MCA double barrel bypass, this surgery can obtain higher STA CFI, while long-term outcomes of patients were the same. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study is to investigate the optimal time window for initiating mobilizing after acute ischemic stroke. Methods The TIME Trial is a pragmatic, investigator-initiated, multi-center, randomized, 3-arm parallel group, clinical trial. This trial will be conducted in 57 general hospitals in mainland China affiliated with the China Stroke Databank Center and will enroll 6033 eligible patients with acute ischemic stroke. Participants will be randomly allocated to either (1) the very early mobilization group in which mobilization is initiated within 24 hours from stroke onset, (2) the early mobilization group in which mobilization begins between 24 and 72 hours poststroke, or (3) the late mobilization group in which mobilization is started after 72 hours poststroke. The mobilization protocol is otherwise standardized and identical for each comparison group. Mobilization is titrated by baseline mobility level and progress of patients throughout the intervention period. The primary outcome is death or disability assessed with the modified Rankin scale at 3 months poststroke. Secondary outcomes include impairment score of the National Institutes of Health Stroke Scale, dependence in activities of daily living as measured using the modified Barthel Index, cognitive ability assessed with the Mini-Mental State Examination, incidence of adverse events, hospital length of stay, and total medical costs. Impact The TIME Trial is designed to answer the question "when is the best time to start mobilization after stroke?" The effect of timing is isolated from the effect of type and dose of mobilization by otherwise applying a standard mobilization protocol across groups. The TIME Trial may, therefore, contribute to increasing the knowledge base regarding the optimal time window for initiating mobilization after acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate the prognostic impact of the burden of new-onset atrial fibrillation (NOAF) on long-term cardiovascular outcomes in patients with acute myocardial infarction (AMI).Methods and Results: This retrospective analysis consecutively included patients without a documented atrial fibrillation (AF) history who admitted for AMI at Shanghai Tenth People's Hospital between February 2014 and March 2018. Atrial fibrillation burden was measured as the percentage of time spent in AF, and its optimal cut-off value of 10.87% was identified by X-tile software. Of 2399 patients (mean age: 65.8 years, 76.6% of men), 278 (11.6%) developed NOAF during hospitalization. During a median follow-up of 2.7 years, the incidence of all-cause death was 3.19, 9.00, and 17.41 per 100 person-years in the sinus rhythm (SR), low-burden (AF burden ≤ 10.87%), and high-burden (AF burden > 10.87%) groups, respectively. After adjustment for confounders, it was the high-burden NOAF [hazard ratio (HR): 1.94, 95% confidence interval (CI): 1.28-2.95] rather than the low-burden one (HR: 1.47, 95% CI: 0.97-2.21) that was significantly associated with increased mortality compared with SR. Concordant results were obtained in our propensity score-matched analyses [2.55 (1.57-4.16) and 1.32 (0.85-2.05) for high- and low-burden NOAF, respectively). In addition, post-myocardial infarction NOAF was associated with an increased risk of heart failure irrespective of its burden. Only those high-burden individuals were at heightened risk of ischaemic stroke. The restricted cubic spline curves illustrated a dose-response relationship of NOAF burden with outcomes.Conclusion: In patients with NOAF complicating AMI, high AF burden was strongly associated with long-term outcomes. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect and safety of Hydroxysafflor Yellow A for Injection (HSYAI) in treating patients with acute ischemic stroke (AIS) and blood stasis syndrome (BSS). Methods: A multicenter, randomized, double-blind, multiple-dose, active-controlled phase II trial was conducted at 9 centers in China from July 2013 to September 2015. Patients with moderate or severe AIS and BSS were randomly assigned to low-, medium-, high-dose HSYAI groups (25, 50 and 70 mg/d HSYAI by intravenous infusion, respectively), and a control group (Dengzhan Xixin Injection (灯盏细辛注射液, DZXXI) 30 mL/d by intravenous infusion), for 14 consecutive days. The primary outcome was the Modified Rankin Scale (mRS) score ⩽1 at days 90 after treatment. The secondary outcomes included the National Institute of Health Stroke Scale (NIHSS) score ⩽1, Barthel Index (BI) score ⩾95, and BSS score reduced ⩾30% from baseline at days 14, 30, 60, and 90 after treatment. The safety outcomes included any adverse events during 90 days after treatment. Results: Of the 266 patients included in the effectiveness analysis, 66, 67, 65 and 68 cases were in the low-, medium-, and high-dose HSYAI and control groups, respectively. The proportions of patients in the medium- and high-dose HSYAI groups with mRS score ⩽1 at days 90 after treatment were significantly larger than the control group (P<0.05). The incidences of favorable outcomes of NIHSS and BI at days 90 after treatment as well as satisfactory improvement of BSS at days 30 and 60 after treatment in the medium- and high-dose HSYAI groups were all significantly higher than the control group (P<0.05). No significant difference was reported among the 4 groups in any specific adverse events (P>0.05). Conclusions: HSYAI was safe and well-tolerated at all doses for treating AIS patients with BSS. The medium (50 mg/d) or high dose (75 mg/d) might be the optimal dose for a phase III trial. (Registration No. ChiCTR-2000029608) [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke is a major public health problem and a main cause of death in China. However, how resting heart rate may associate with ischemic stroke among patients with hypertension remains unclear.Objective: To investigate the association between resting heart rate and ischemic stroke among elderlies with hypertension in China.Methods: We conducted a retrospective study of elderlies with hypertension who aged ≥60 years and were free from a stroke at baseline. Resting heart rate at baseline was treated as both continuous and categorical variable. Hazard ratios for ischemic stroke were estimated by multivariate Cox proportional hazards models.Results: A total of 3071 elderlies with hypertension [1369 (44.6%) men, an average age of 71.3 ± 7.1 years] were enrolled, and 182 cases of ischemic stroke occurred during a mean follow-up period of 5.5 years. Multivariate Cox regression showed that every 10 bpm increment in resting heart rate elevated the risk of ischemic stroke by 21% (95%CI: 1.05, 1.73; P = 0.018). After adjusting for confounders, resting heart rate ≥90 bpm significantly associated with the risk of ischemic stroke (HR: 1.35, 95% CI = 1.16, 2.78) when using the resting heart rate <60 bpm as a referent. Subgroup analysis showed that the relation between resting heart rate and risk of ischemic stroke was seem to be stronger in female (HR: 1.32 vs 1.11), those with uncontrolled hypertension (HR: 1.32 vs 1.12), people with combined diabetes and hypertension (HR: 1.31 vs 1.12), people with overweight (HR: 1.39 vs 1.02) and those who aged >75 (HR: 1.33 vs 1.11). Smoothing spline plots suggested the optimal resting heart rate for the lowest risk of ischemic stroke was between 60 and 80 bpm.Conclusions: In Chinese elderly hypertensive patients, elevated resting heart rate was an independent predictor of ischemic stroke, and the optimal resting heart rate was around 70 bpm. [ABSTRACT FROM AUTHOR]

Introduction: Incontinentia pigmenti (IP) is a rare neuroectodermal dysplasia caused by a defect in the IKBKG gene. The pathogenesis of central nervous system injury is believed to be related to microvascular ischemia. Currently, few treatment strategies are available for the inflammatory phase., Materials and Methods: This retrospective descriptive analysis included the clinical data of 41 children with IP collected from 2007 to 2021 in Xi'an, China, comprising clinical characteristics, imaging findings, blood cell analysis, skin histopathology, and genetic data., Results: Fourteen children (34%) aged 4 days to 5 months exhibited clinical signs and symptoms, including convulsions, delayed psychomotor development following neurological damage, and revealed significant MRI abnormalities, including ischemia, hypoxia, cerebral hypoperfusion, hemorrhage, encephalomalacia, and cerebral atrophy. Eight of the 24 patients (33%) presented with retinal vascular tortuosity and telangiectasis, accompanied by neovascularization and hemorrhage. Thirty-eight children (93%) had elevated eosinophils (mean: 3.63 ± 4.46 × 10 9 ), and 28 children (68%) had significantly elevated platelets (mean: 420.16 ± 179.43 × 10 9 ). Histopathology of skin revealed microvascular extravasation and vasodilation with perivascular and intravascular eosinophilic infiltration., Conclusion: Brain injury in IP occurs during infancy until 5 months of age, which is also the acute dermatitis phase accompanied by eosinophilia and an increased platelet count. This study provides evidence of microvascular damage to the skin and fundus during the inflammatory phase. The mechanism of microvascular damage may be similar to that in the brain., (© 2024. The Author(s).)

Background: Previous randomised trials have shown an overwhelming benefit of mechanical thrombectomy for treating patients with stroke caused by large vessel occlusion of the anterior circulation. Whether endovascular treatment is beneficial for vertebrobasilar artery occlusion remains unknown. In this study, we aimed to investigate the safety and efficacy of endovascular treatment of acute strokes due to vertebrobasilar artery occlusion.Methods: We did a multicentre, randomised, open-label trial, with blinded outcome assessment of thrombectomy in patients presenting within 8 h of vertebrobasilar occlusion at 28 centres in China. Patients were randomly assigned (1:1) to endovascular therapy plus standard medical therapy (intervention group) or standard medical therapy alone (control group). The randomisation sequence was computer-generated and stratified by participating centres. Allocation concealment was implemented by use of sealed envelopes. The primary outcome was a modified Rankin scale (mRS) score of 3 or lower (indicating ability to walk unassisted) at 90 days, assessed on an intention-to-treat basis. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial haemorrhage, device-related complications, and other severe adverse events. The BEST trial is registered with ClinicalTrials.gov, NCT02441556.Findings: Between April 27, 2015, and Sept 27, 2017, we assessed 288 patients for eligibility. The trial was terminated early after 131 patients had been randomly assigned (66 patients to the intervention group and 65 to the control group) because of high crossover rate and poor recruitment. In the intention-to-treat analysis, there was no evidence of a difference in the proportion of participants with mRS 0-3 at 90 days according to treatment (28 [42%] of 66 patients in the intervention group vs 21 [32%] of 65 in the control group; adjusted odds ratio [OR] 1·74, 95% CI 0·81-3·74). Secondary prespecified analyses of the primary outcome, done to assess the effect of crossovers, showed higher rates of mRS 0-3 at 90 days in patients who actually received the intervention compared with those who received standard medical therapy alone in both per-protocol (28 [44%] of 63 patients with intervention vs 13 [25%] of 51 with standard therapy; adjusted OR 2·90, 95% CI 1·20-7·03) and as-treated (36 [47%] of 77 patients with intervention vs 13 [24%] of 54 with standard therapy; 3·02, 1·31-7·00) populations. The 90-day mortality was similar between groups (22 [33%] of 66 patients in the intervention vs 25 [38%] of 65 in the control group; p=0·54) despite a numerically higher prevalence of symptomatic intracranial haemorrhage in the intervention group.Interpretation: There was no evidence of a difference in favourable outcomes of patients receiving endovascular therapy compared with those receiving standard medical therapy alone. Results might have been confounded by loss of equipoise over the course of the trial, resulting in poor adherence to the assigned study treatment and a reduced sample size due to the early termination of the study.Funding: Jiangsu Provincial Special Program of Medical Science. [ABSTRACT FROM AUTHOR]

Background: In China, the combination of herb Salvia miltiorrhiza Bge. (Danshen) and Carthamus tinctorius L. (Honghua) is an effective treatment for stroke. A previous study showed that the combination of four herbal components: danshensu (DSS), hydroxysafflor yellow A (HSYA), salvianolic acid A (SAA), and salvianolic acid B (SAB) was effective for treatment of cerebral ischemia-reperfusion (I/R) injury in rats. However, the pharmacokinetic characteristics of this formula require further investigation. The present study investigated the pharmacokinetic differences between each component of in two formulas in cerebral I/R injury rats. The influencing factors may affect the compatibility of components were analyzed. Methods: Focal cerebral I/R was induced by middle cerebral artery occlusion (MCAO). Rats that underwent MCAO were randomly divided into two groups and administered treatments through the tail vein. Blood samples were collected at predetermined time points following administration. The concentrations of DSS, HSYA, SAB, and SAA in rat plasma were determined using HPLC-DAD, and the main pharmacokinetic parameters were calculated. Pharmacokinetic parameters were calculated using DAS 3.2.6 software and SPSS 23.0 statistical analysis software. Results: Our results showed that DSS, HSYA, SAB, and SAA in MCAO model rats had statistically significant differences in two formulas. For DSS and SAA, pharmacokinetic parameters with statistically significant differences including AUC(0−t), AUMC(0−t), MRT(0−t), VRT(0−t), t1/2z, Vz, CLz, and Cmax (P < 0.01). For HSYA, significant differences in the parameters including AUC(0−t), AUMC(0−t), MRT(0−t), VRT(0−t) (P < 0.01), CLz and Cmax (P < 0.05). Conclusion: The difference in pharmacokinetic parameters in response to each component may have been due to differences in the dosages of the components (HSYA, SAA, SAB) and the compatibility of components. Meanwhile, there were many influencing factors could affect the compatibility of components, such as the metabolism by CYP450 enzymes, plasma protein binding rates, and effects related to the blood-brain barrier (BBB). Moreover, our study provided new insights, such as choosing appropriate dosages of active components of traditional Chinese medicine (TCM) to aid in prevention and treatment of cerebral ischemic diseases. The method and results in this study could provide a foundation for future pharmacological studies of the active components in Danshen and Honghua. [ABSTRACT FROM AUTHOR]

Dl-3-n-butylphthalide (dl-NBP) was approved by the FDA of China for the treatment of acute ischemic stroke. Dl-NBP has been shown to promote neurological functional recovery and enhance white matter integrity using an endothelin-1-induced focal permanent cerebral ischemia model, which could mimic those patients who have no opportunity to receive either tissue plasminogen activator (tPA) thrombolysis or endovascular therapy. However, it is not clear whether dl-NBP could promote neurological functional recovery in a focal transient cerebral ischemia model, which could mimic those patients who have the opportunity to receive either tPA thrombolysis or endovascular therapy. In this study, using a model of middle cerebral artery occlusion in mice, we aim to explore the effect of two-week dl-NBP treatment on neurological functional recovery after ischemic stroke as well as its underlying mechanism. Our results showed that dl-NBP treatment promoted functional recovery assessed by neurological scores and an adhesive remove test, and this improved the integrity of white matter after 60-min ischemia and 14-day reperfusion. In addition, dl-NBP increased the number of RECA-1 positive vessels and enhanced the expression of the tight junction protein occludin. More importantly, dl-NBP also promoted the expression of hypoxia-induced factor-1α, the vascular endothelial growth factor, Notch, and delta-like ligand 4. In conclusion, our study provides evidence that dl-NBP treatment could also promote functional recovery after focal transient ischemia stroke, and this recovery is associated with upregulated white matter integrity, microvessels, and the tight junction protein occludin. Our results suggested that, in future, dl-NBP may also be applied in clinic to promote functional recovery during the later phase of focal transient ischemic stroke. [ABSTRACT FROM AUTHOR]

The association between blood pressure and intracranial artery stenosis (ICAS) in different age groups has not been elucidated. Using data from the "China Hypertension Survey," we conducted a cross-sectional analysis of the association between blood pressure parameters and ICAS. In this study, participants older than 35 years were selected by stratified, multistage random sampling. Blood pressure was measured repeatedly at rest, and ICAS was assessed by transcranial doppler ultrasound. Binary logistic regression analysis was used to demonstrate the association between different blood pressure indicators and ICAS. Of the 3640 participants included (mean age 63 ± 13 years old, 57.8% female), systolic blood pressure (SBP) and pulse pressure (PP) were associated with ICAS in the general population; the multivariable adjusted odds ratio (OR) and corresponding 95% confidence interval (95% CI) of ICAS and multivessel stenosis were 1.32 (1.21, 1.45) and 1.29 (1.14, 1.46) per standard deviation (SD) increase in SBP and 1.44 (1.30, 1.59) and 1.52 (1.33, 1.74) for PP, respectively. Further analysis of this association in different age groups revealed inconsistent results between SBP and ICAS. Prehypertension (120 ≤ SBP < 140) could predict ICAS in the older group but not in the younger group, and the positive association between SBP and multivessel stenosis disappeared in the younger age group (P > .05 in all SBP subgroups). In conclusion, SBP and PP could not only identify ICAS in the middle-aged and elderly population but could also provide some information about ICAS burden; however, these associations need to be interpreted differentially based on age subgroup. [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate the safety of discontinuing oral anticoagulation (OAC) therapy after apparently successful atrial fibrillation (AF) ablation, using data from the Chinese Atrial Fibrillation Registry study.Methods and Results: We identified 4512 consecutive patients who underwent successful AF ablation between August 2011 and December 2017. Of them, 3149 discontinued OAC 3 months post-ablation (Off-OAC group) and 1363 continued OAC beyond this period (On-OAC group). Regular follow-up examinations were undertaken to detect AF recurrence, monitor OAC therapy, and measure clinical outcomes. Primary outcomes included thromboembolic and major bleeding (MB) events experienced beyond 3 months after ablation. Low thromboembolic and MB event rates were noted in the on-treatment analysis. The incidence rates for thromboembolism were 0.54 [95% confidence interval (CI) 0.39-0.76] and 0.86 (95% CI 0.56-1.30) per 100 patient-years, and that for MB events were 0.19 (95% CI 0.11-0.34) and 0.35 (95% CI 0.18-0.67) per 100 patient-years, for the Off-OAC and On-OAC groups over mean follow-up periods of 24.2 ± 14.7 and 23.0 ± 13.6 months, respectively. Similar results were observed in the intention-to-treat analysis. Previous history of ischaemic stroke (IS)/transient ischaemic attack (TIA)/systemic embolism (SE) [hazard ratio (HR) 3.40, 95% CI 1.92-6.02; P < 0.01] and diabetes mellitus (HR 2.06, 95% CI 1.20-3.55, P = 0.01) were independently associated with thromboembolic events, while OAC discontinuation (HR 0.71, 95% CI 0.41-1.23, P = 0.21) remained insignificant in multivariable analysis.Conclusions: This study suggests that it may be safe to discontinue OAC in post-ablation patients under diligent monitoring, in the absence of AF recurrence, history of IS/TIA/SE, and diabetes mellitus. However, further large-scale randomized trials are required to confirm this.Trial Registration: Chinese Clinical Trial Registry ChiCTR-OCH-13003729. URL: http://www.chictr.org.cn/showproj.aspx?proj=5831. [ABSTRACT FROM AUTHOR]

According to the research progress in recent years, "Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2018" has greatly revised and supplemented the criteria for the diagnosis and treatment of acute ischemic stroke. Based on the new clinical research evidence published in the past four years, this paper interprets the revisions and supplements of the guidelines 2018. [ABSTRACT FROM AUTHOR]

Microglia participate in bi-directional control of brain repair after stroke. Previous studies have demonstrated that hydrogen protects brain after ischemia/reperfusion (I/R) by inhibiting inflammation, but the specific mechanism of anti-inflammatory effect of hydrogen is poorly understood. The goal of our study is to investigate whether inhalation of high concentration hydrogen (HCH) is able to attenuate I/R-induced microglia activation. Eighty C57B/L male mice were divided into four groups: sham, I/R, I/R + HCH and I/R + N2/O2 groups. Assessment of animals happened in "blind" matter. I/R was induced by occlusion of middle cerebral artery for one hour). After one hour, filament was withdrawn, which induced reperfusion. Hydrogen treated I/R animals inhaled mix of 66.7% H2 balanced with O2 for 90 minutes, starting immediately after initiation of reperfusion. Control animals (N2/O2) inhaled mix in which hydrogen was replaced with N2 for the same time (90 minutes). The brain injury, such as brain infarction and development of brain edema, as well as neurobehavioral deficits were determined 23 hours after reperfusion. Effect of HCH on microglia activation in the ischemic penumbra was investigated by immunostaining also 23 hours after reperfusion. mRNA expression of inflammation related genes was detected by PCR. Our results showed that HCH attenuated brain injury and consequently reduced neurological dysfunction after I/R. Furthermore, we demonstrated that HCH directed microglia polarization towards anti-inflammatory M2 polarization. This study indicates hydrogen may exert neuroprotective effects by inhibiting the microglial activation and regulating microglial polarization. This study was conducted in agreement with the Animal Care and Use Committee (IACUC) and Institutional Animal Care guidelines regulation (Shanghai Jiao Tong University, China (approval No. A2015-011) in November 2015. [ABSTRACT FROM AUTHOR]

Objective To analyze the epidemiological characteristics of neurosyphilis in Tianjin Huanhu Hospital. Methods The epidemiological data, laboratory examination results and neuroimaging features of 138 patients with neurosyphilis who were diagnosed and treated in our hospital from 2012 to 2017 were retrospectively analyzed. Results All patients were divided into asymptomatic neurosyphilis (asymptomatic group, N = 32), interstitial neurosyphilis (interstitial group, N = 46) and parenchymatous neurosyphilis (parenchymatous group, N = 60). The proportion of male patients (χ2 = 9.623, P = 0.002; χ² = 7.953, P = 0.005) and age (t = 2.985, P = 0.004; t = 3.322, P = 0.001) of parenchymatous group were higher than those of asymptomatic group and interstitial group. The rapid plasma reagin (RPR) titers of interstitial group (Z = 2.394, P = 0.024) and parenchymatous group (Z = 2.937, P = 0.004) were higher than that of asymptomatic group. The protein quantification of parenchymatous group was higher than that of asymptomatic group (t = 2.453, P = 0.017). The imaging findings of patients in asymptomatic group showed no abnormalities. The imaging findings of 22 patients in interstitial group showed cerebral infarction, while the other one did not show abnormality. The imaging findings of 28 patients in parenchymatous group showed abnormalities such as cerebral ischemia, white matter degeneration, demyelination and hydrocephalus, while the other 7 patients did not show abnormality. Conclusions Neurosyphilis is more common in men and lower education people, which has complex and diverse clinical features and imaging manifestations. It is necessary to strengthen the measures of health education and behavior intervention in high-risk population, so as to reduce the incidence of neurosyphilis. [ABSTRACT FROM AUTHOR]

Background: Identification of novel risk factors is needed to further lower stroke risk. Data concerning the association between plasma retinol concentrations and the risk of stroke are limited. Objectives: We aimed to evaluate the effect of plasma retinol on the risk of first stroke and to examine any possible effect modifiers in hypertensive patients. Methods: The study sample population was drawn from the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, including 620 cases with first stroke and 620 matched controls. In the CSPPT, a total of 20,702 hypertensive patients were randomly assigned to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. The median treatment duration was 4.5 y. Results: There was a significant inverse association between plasma retinol and the risk of first stroke (per 10-μg/dL increment; OR: 0.92; 95% CI: 0.86, 0.97) and first ischemic stroke (OR: 0.92; 95% CI: 0.86, 0.98). When retinol was assessed as quartiles, significantly lower risks of first stroke (OR: 0.64; 95% CI: 0.46, 0.88) and first ischemic stroke (OR: 0.67; 95% CI: 0.46, 0.96) were found in participants in quartiles 2–4 compared with those in quartile 1. Furthermore, a stronger inverse association between plasma retinol and first stroke was observed in participants with baseline total homocysteine (<10 compared with ≥10 μmol/L; P-interaction = 0.049). However, plasma retinol had no significant effect on first hemorrhagic stroke (per 10-μg/dL increment; OR: 0.98; 95% CI: 0.79, 1.18). Conclusions: Our data showed a significant inverse association between plasma retinol and the risk of first stroke among Chinese hypertensive adults. [ABSTRACT FROM AUTHOR]

Objective: It is unknown whether prediabetes is a predictor of poststroke depression (PSD). We aimed to explore the relationship between prediabetes and PSD in Chinese patients with acute ischemic stroke.Methods: This is a prospective cohort study, and a total of 358 patients with acute ischemic stroke were recruited and enrolled. Patients were divided into 3 groups: normal glucose group (NGT, n = 96), prediabetes group (preDM, n = 134, impaired fasting glucose (IFG), and/or impaired glucose tolerance (IGT) and/or HbA1c (A1c) 5.7%-6.4%), and the diabetes mellitus group (DM, n = 128). At 1 month after stroke, patients with a Hamilton Depression Scale score of ≥8 were diagnosed as PSD.Results: In post hoc comparisons, the risk of PSD in patients with diabetes and prediabetes was higher than patients with NGT (37.5% vs 31.3% vs 14.6%, P = .001). Compared with NGT, the incidence rate of PSD in patients with prediabetes with HbA1c 5.7% to 6.4% and patients with prediabetes with IFG/IGT + HbA1c 5.7% to 6.4% was higher (35.3% vs 14.6%, 38.0% vs 14.6%; P = .006; P = .003, respectively). In logistic regression, prediabetes with HbA1c 5.7% to 6.4% and prediabetes with IFG/IGT + HbA1c 5.7% to 6.4% were a significant independent predictor of PSD after adjusting for potential confounding factors, with odd ratios of 1.731 and 1.978, respectively.Conclusions: Our study showed that prediabetes was associated with PSD and may predict its development at 1 month poststroke. In prediabetes subgroups, patients with HbA1c 5.7% to 6.4% were more likely to develop PSD compared to NGT and IFG/IGT groups. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment for patients with ischaemic stroke with a high risk of cerebral haemorrhage is unclear. We assessed the efficacy and safety of cilostazol versus aspirin, with and without probucol, in these patients.Methods: In this randomised, controlled, 2 × 2 factorial trial, we enrolled patients with ischaemic stroke with a history of or imaging findings of intracerebral haemorrhage or two or more microbleeds from 67 centres in three Asian countries. Patients were randomly assigned (1:1:1:1) to receive oral cilostazol (100 mg twice a day), aspirin (100 mg once a day), cilostazol plus probucol (250 mg twice a day), or aspirin plus probucol with centralised blocks stratified by centre. Cilostazol versus aspirin was investigated double-blinded; probucol treatment was open-label, but the outcome assessor was masked to assignment. The co-primary outcomes were incidence of the composite of stroke, myocardial infarction, or vascular death (efficacy) and incidence of haemorrhagic stroke (safety), which were assessed in intention-to-treat and modified intention-to-treat populations. Efficacy was analysed with a non-inferiority test and a superiority test if non-inferiority was satisfied. Safety was assessed with a superiority test only. This trial is registered with ClinicalTrials.gov, NCT01013532.Findings: Between Aug 1, 2009, and Aug 31, 2015, we randomly assigned 1534 patients to one of the four study groups, of whom 1512 were assessed for the co-primary endpoints. During a median follow-up of 1·9 years (IQR 1·0-3·0), the incidence of composite vascular events was 4·27 per 100 person-years in patients who received cilostazol and 5·33 per 100 person-years in patients who received aspirin (HR 0·80, 95% CI 0·57-1·11; non-inferiority p=0·0077; superiority p=0·18). Incidence of cerebral haemorrhage was 0·61 per 100 person-years in patients who received cilostazol and 1·20 per 100 person-years in those who received aspirin (HR 0·51, 97·5% CI 0·20-1·27; superiority p=0·18). The incidence of vascular events was 3·91 per 100 person-years in the probucol group compared with 5·75 per 100 person-years in the non-probucol group (HR 0·69, 95% CI 0·50-0·97; superiority p=0·0316). The incidence of cerebral haemorrhage was 0·72 per 100 person-years in the probucol group and 1·11 per 100 person-years in the non-probucol group (HR 0·65, 97·5% CI 0·27-1·57; p=0·55). Adverse events were similar across the four study groups; the most common events were dizziness, headache, diarrhoea, and constipation.Interpretation: In patients with ischaemic stroke at high risk of cerebral haemorrhage, cilostazol was non-inferior to aspirin for the prevention of cardiovascular events, but did not reduce the risk of haemorrhagic stroke. Addition of probucol to aspirin or cilostazol could be beneficial for reducing the incidence of cardiovascular events.Funding: Korea Otsuka Pharmaceutical. [ABSTRACT FROM AUTHOR]