Femoral access was associated with subsequent stroke or TIA compared to radial access (OR 2.10 [1.30-3.39], p<0.002). Previous stroke/TIA was associated with subsequent stroke/TIA (p<0.001), death (p<0.001) and MI (p=0.002). Furthermore, subsequent stroke/TIA was significantly associated with subsequent MI (p=0.006), congestive cardiac failure (CCF) (p=0.008) and death (p<0.001).

In patients undergoing non-emergency PCI, previous stroke/TIA predicted post-PCI ischaemic stroke/TIA, which was associated with death, MI, CCF.

In patients undergoing non-emergency PCI, previous stroke/TIA predicted post-PCI ischaemic stroke/TIA, which was associated with death, MI, CCF.

Duplication of the middle cerebral artery (DMCA) is an anomalous vessel arising from the internal carotid artery (ICA). Aneurysms at the origin of a DMCA have been reported; however, most have been treated with clipping surgery. Here, we describe two cases of aneurysms at the origin of a DMCA treated with coil embolization.

Case 1 A seventy-three year-old man presented with severe headache and was diagnosed with subarachnoid hemorrhage (SAH). Digital subtraction angiography (DSA) and 3-dimensional (3-D) DSA showed an aneurysm arising from a DMCA. Coil embolization was performed with DMCA patency. The patient had an uneventful postoperative course. CASE 1 A 44-year-old woman presented with a history of clipping for an IC-anterior choroidal artery (AchA) aneurysm 8 years prior. Magnetic resonance imaging (MRI) showed regrowth of the aneurysm. 3-D DSA showed an IC-DMCA aneurysm located laterally and distal to the AchA. The DMCA arose from the bottom of the aneurysm. Coil embolization was performed without DMCA occlusion and showed no postoperative ischemic changes.

An IC-DMCA aneurysm is rare and may be misdiagnosed as an AchA aneurysm. Clinicians should perform a 3D-DSA evaluation if the aneurysm arises from the lateral wall of the IC to obtain a precise diagnosis and to preserve the DMCA during coil embolization.

An IC-DMCA aneurysm is rare and may be misdiagnosed as an AchA aneurysm. Clinicians should perform a 3D-DSA evaluation if the aneurysm arises from the lateral wall of the IC to obtain a precise diagnosis and to preserve the DMCA during coil embolization.Specificity and sensitivity in biochemical reactions can be achieved through regulation of equilibrium binding affinity or through proofreading mechanisms that allow for the dissociation of unwanted intermediates. In this essay, we aim to provide our perspectives on how the concept of kinetic proofreading might apply in the context of cargo sorting in clathrin-mediated endocytosis.

Although intravenous thrombolysis (IVT) is recommended among acute ischemic stroke (AIS) patients secondary to large vessel occlusion (LVO) undergoing mechanical thrombectomy (MT), time delays with bridging therapy (IVT prior to MT) and its potential benefit remains unclear. We compared the time delays and clinical outcomes among AIS SECONDARY TO LVO patients treated with bridging therapy or direct MT (dMT) at a comprehensive stroke center (CSC).

We performed a retrospective analysis of prospectively collected data of AIS secondary to LVO patients admitted between 2012 and 2017 at a large volume CSC. AIS secondary to LVO patients arriving directly from field to CSC within 4.5h were included. Demographic characteristics, clinical and radiological data, treatment and procedural information were extracted and analyzed.

Among 777 AIS secondary to LVO patients treated with MT, 237 patients (156 dMT, 81 bridging therapy) were included. Mean age was 70.3 year-old, median NIHSS score was 18, and door-to-needle time was 40min (IQR 31-56min). The median door-to-puncture (DTP) time was 22min longer in bridging therapy group in comparison to dMT group, 74 vs 52min (p<0.001). Additionally, no difference was observed between the groups for successful recanalization or functional independence.

At a large volume CSC, bridging therapy (vs. dMT) was observed to have a longer DTP time without any difference in successful recanalization or clinical outcomes.

At a large volume CSC, bridging therapy (vs. dMT) was observed to have a longer DTP time without any difference in successful recanalization or clinical outcomes.Involvement of the bone matrix protein osteocalcin (OC) in the development of learning and memory, and the prevention of anxiety-like behaviors in mice. However, the direct effects of OC on neurons are still unknown comparing to the mechanism how OC affects systemic energy expenditure and glucose homeostasis. In this study, we investigated the effect of OC on proliferation, differentiation, and survival of neurons using the rat pheochromocytoma cell line PC12. RT-PCR analysis for OC receptor candidates revealed that Gpr158, but not Gprc6a, mRNA was expressed in PC12 cells. The growth of PC12 cells cultured in the presence of 5-50 ng/mL of either uncarboxylated (GluOC) or carboxylated (GlaOC) OC was increased compared to cells cultured in the absence of OC. In addition, NGF-induced neurite outgrowth was enhanced by OC, and H2O2-induced cell death was suppressed by pretreatment with OC. All of these results were observed for both GluOC and GlaOC at comparable levels, suggesting that OC may directly affect cell proliferation, differentiation, and survival by binding to its candidate receptor, GPR158.

Renal ischemia reperfusion injury (IRI) has become a growing concern in clinical practice with high morbidity and mortality rates. There is currently no effective prophylactic regimen available to prevent its occurrence and to improve its clinical prognosis. Dl-3-n-butylphthalide (NBP) has been used for stroke treatment in China for years. Little is known about its role in preventing kidney injury.

The kidneys of male C57BL/6J mice were subjected to 33min of ischemia followed by 24h of reperfusion. NBP was administered by gavage prior to surgery. The reno-protective effect of NBP was evaluated by serum creatinine, kidney injury markers and renal pathological changes. Furthermore, the inflammation, oxidative stress, and apoptosis markers in kidney tissue were examined. Invitro, HK2 cells were treated prophylactically with NBP and then exposed to hypoxia/reoxygenation (H/R). Cell viability and apoptosis related protein were quantified to verify the protective effect of NBP. Pro-inflammation genes expression as well as ROS generation were further investigated also.

NBP pretreatment significantly improved renal dysfunction and alleviated pathological injury, renal inflammation response, oxidative stress and cell apoptosis. Consistently, NBP attenuated H/R induced increases in ROS, pro-inflammatory genes expression, apoptosis and cleaved caspase-3 levels in HK2 cells.

Our promising results validated for the first time that NBP could ameliorate renal IRI via attenuating inflammation, oxidative stress, and apoptosis, which indicated that NBP might be a good candidate against AKI.

Our promising results validated for the first time that NBP could ameliorate renal IRI via attenuating inflammation, oxidative stress, and apoptosis, which indicated that NBP might be a good candidate against AKI.Studies have shown that the specific entry of peripheral cells into the brain parenchyma caused by BBB injury and the imbalance of the immune microenvironment in the brain are closely related to the pathogenesis of Alzheimer’s disease (AD). Because of the difficulty of obtaining data inside the brain, it is urgent to find out the relationship between the peripheral and intracerebral data and their influence on the development of AD by machine learning methods. However, in the actual algorithm design, it is still a challenge to extract relevant information from a variety of data to establish a complete and accurate regulatory network. In order to overcome the above difficulties, we presented a method based on a message passing model (Passing Attributes between Networks for Data Assimilation, PANDA) to discover the correlation between internal and external brain by the BBB injury-related genes, and further explore their regulatory mechanism of the brain immune environment for AD pathology. The Biological analysis of the results showed that pathways such as immune response pathway, inflammatory response pathway and chemokine signaling pathway are closely related to the pathogenesis of AD. Especially, some significant genes such as RELA, LAMA4, PPBP were found play certain roles in the injury of BBB and the change of permeability in AD patients, thus leading to the change of immune microenvironment in AD brain.Towards repairing bone defects, calcium sulfate and calcium phosphate cement have been recognized as promising bone grafts. However, the current bone cements are generally lack of proper porosity for cell migration and new tissue formation. On the other hand, porous scaffold cannot be delivered by injection, which limits its use its clinical use. Herein, we develop a novel tricalcium phosphate/calcium sulfate granule to overcome the limitations of injectable cements and traditional scaffolds. The biocompatible granule underwent in situ self-setting to form scaffold with porous structure after injection. It contributes to calcium deposition and upregulation of osteogenic genes of mesenchymal stem cells in a time-dependent manner. Within three months, cavitary bone defects of distal rabbit femurs implanted the granules exhibited better bone formation than those with those implanted with autologous bone.Hypoxia-inducible factor 2 (HIF-2), is essential for cellular response to hypoxia and holds an important role in erythropoiesis, angiogenesis, tissue invasion and metastasis, thus, constituting an important therapeutic target. Maximal HIF-2 transcriptional activation requires HIF-2α phosphorylation by ERK1/2 that impairs its CRM1-mediated nuclear export. Herein, we reveal a novel interaction of HIF-2α with Reptin52, a multifunctional protein involved in cellular functions orchestrated both in the nucleus and the cytoplasm. HIF-2α and Reptin52 interact both in nuclear and cytoplasmic fractions, however, ERK1/2 pathway inactivation seems to favour their association in the cytoplasm. Notably, we demonstrate that Reptin52 reduces HIF-2 transcriptional activity, which results in decreased EPO secretion under hypoxia, by impairing HIF-2α stability via a non-canonical PHD-VHL-proteasome independent mechanism. This interaction represents a novel HIF-2 fine tuning mechanism that allows for distinct HIF1/2 isoforms regulation.Gastric cancer (GC) is the most common cancer worldwide. Although advances in the treatments, the oncogenic mechanisms are still largely unknown. RNF168 (ring-finger nuclear factor 168) is an important regulator of DNA double-strand break (DSB) repair, and its defects have been involved in the pathogenesis of a number of human diseases including cancer. However, its effects on GC are still unclear. In the study, we demonstrated that RNF168 expression was remarkably down-regulated in human GC tissues, and its low expression showed worse overall survival rate in GC patients. Importantly, we here reported that RNF168 directly interacted with Ras homolog gene family member C (RHOC) and induced its ubiquitination to promote RHOC degradation. RHOC exhibited higher expression in human GC tissues, and its knockdown significantly restrained cell proliferation, migration and invasion in GC cell lines. Moreover, RHOC knockdown led to a significant reduction in GC tumor growth in a xenograft mouse model. Additionally, histone deacetylase 1 (HDAC1) was found to be markedly decreased in GC cells with RHOC knockdown.