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This multicenter, open-label, randomized study (Registration No. ChiCTR-OCH-14004528) aimed to compare the efficacy and effects of oxcarbazepine (OXC) with levetiracetam (LEV) as monotherapies on patient quality of life and mental health for patients with newly diagnosed focal epilepsy from China.Patients with newly diagnosed focal epilepsy who had experienced 2 or more unprovoked seizures at greater than a 24-h interval during the previous year were recruited. Participants were randomly assigned to the OXC group or LEV group. Efficacy, safety, quality of life, and mental health were evaluated over 12-week and 24-week periods.In total, we recruited 271 newly diagnosed patients from 23 centers. Forty-four patients were excluded before treatment for reasons. The rate of seizure freedom of OXC was significantly superior to that of LEV at 12 weeks and 24 weeks (p 0.05). The quality of life (except for the seizure worry subsection) and anxiety scale scores also showed significant differences from before to after treatment in the OXC and LEV groups.OXC monotherapy may be more effective than LEV monotherapy in patients with newly diagnosed focal epilepsy. Both OXC and LEV could improve the quality of life and anxiety state in adult patients with focal epilepsy.

Background and Purpose: Whether imaging parameters would independently predict stroke recurrence in low-risk minor ischemic stroke (MIS) or transient ischemic attack (TIA) according to traditional score system (such as ABCD 2 score, which was termed on the basis of the initials of the five factors: age, blood pressure, clinical features, duration, diabetes) remains unclear. We sought to evaluate the association between imaging parameters and 1-year stroke recurrence in patients with TIA or MIS in different risk stratum stratified by ABCD 2 score. Methods: We included patients with TIA and MIS (National Institutes of Health Stroke Scale score ≤3) with complete baseline vessel and brain imaging data from the Third China National Stroke Registry III. Patients were categorized into different risk groups based on ABCD 2 score (low risk, 0–3; moderate risk, 4–5; and high risk, 6–7). The primary outcome was stroke recurrence within 1 year. Multivariable Cox proportional-hazards regression models were used to assess whether imaging parameters (large artery stenosis, infarction number) were independently associated with stroke recurrence. Results: Of the 7140 patients included, 584 patients experienced stroke recurrence within 1 year. According to the ABCD 2 score, large artery stenosis was associated with higher stroke recurrence in both low-risk (adjusted hazard ratio, 1.746 [95% CI, 1.200–2.540]) and moderate-risk group (adjusted hazard ratio, 1.326 [95% CI, 1.042–1.687]) but not in the high-risk group ( P >0.05). Patients with multiple acute infarctions or single acute infarction had a higher risk of recurrent stroke than those with no infarction in both low- and moderate-risk groups, but not in the high-risk group. Conclusions: Large artery stenosis and infarction number were independent predictors of 1-year stroke recurrence in low-moderate risk but not in high-risk patients with TIA or MIS stratified by ABCD 2 score. This finding emphasizes the importance of early brain and vascular imaging evaluation for risk stratification in patients with TIA or MIS.

Background To determine treatment effects on the incidence of post-stroke epilepsy (PSE) using different doses of statin, a prospective hospital-based cohort study was designed to explore whether a double-dose statin treatment can better prevent the occurrence of PSE. Methods A total of 1152 patients with newly diagnosed ischemic stroke admitted to our hospital from March to August 2017 were selected, 1033 of whom were followed-up. Patients were divided into two treatment groups:(1) standard-dose (20 mg atorvastatin or 10 mg rosuvastatin,daily oral; 788 patients); and (2) double-dose (40 mg atorvastatin or 20 mg rosuvastatin, daily oral; 245 patients).At 18 months follow-up was conducted to compare the incidence of PSE between groups. Results In general, in the standard-dose group we observed two cases of early seizure (ES) (0.25%), 22 cases oflate seizure (LS) (2.79%) and 20 cases of PSE (2.54%). In the double-dose group, onepatient had ES (0.41%), two patients had LS (0.82%), and onepatient had PSE (0.41%). The incidence of PSE was significantly lower in the double-dose group as compared to the standard-dose group. There was a higher proportion of PSE in patients younger than 65 years and in males. Three patients had ES; one presented with focal aware seizure (FAS), and two had focal to bilateral tonic-clonic seizure (FBTCS). Among the 21 patients with PSE, there were two cases of FAS, five cases of focal impaired awareness seizure (FIAS), five cases of FBTCS, and nine cases of GTCS, suggesting that partial seizure is the most common type of PSE. Cerebral cortex was involved in 85.75% of cases with PSE, and multiple lobes were involved in 61.9% of cases with PSE. Conclusion Increasing the dose of statin treatment during the acute phase of ischemic stroke reduces the incidence of PSE. Further research is needed to understand the mechanisms underlying the potential preventative effects of statins against PSE.

To investigate the impact of the COVID-19 outbreak on the behaviours, mental health and seizure control of adult patients with epilepsy (PWE) and to identify the correlation of seizure increase and the COVID-19 outbreak to guide the medical care of individuals with epilepsy during a public health crisis.This study was conducted at 28 centres from February 2020 to April 2020. Participants filled out a 62-item online survey including sociodemographic, COVID-19-related, epilepsy-related and psychological variables and were divided into two groups based on whether their seizure frequency increased during the COVID-19 pandemic. Chi-square tests and t-tests were used to test differences in significant characteristics. Multiple logistic regression analyses were used to identify risk factors for seizure worsening.A total of 1,237 adult PWE were enrolled for analysis. Of this sample, 31 (8.33%) patients experienced an increase in seizures during the pandemic. Multivariate logistic regression suggested that feeling nervous about the pandemic (P0.05), poor quality of life (P = 0.001), drug reduction/withdrawal (P = 0.032), moderate anxiety during the COVID-19 outbreak (P = 0.046) and non-seizure free before the COVID-19 outbreak (P0.05) were independently related to seizure increase during the pandemic.During the COVID-19 pandemic, PWE with poor quality of life and mental status, as well as AED reduction/withdrawal, were more likely to experience seizure increase. This observation highlights the importance of early identification of the population at high risk of seizure worsening and implementation of preventive strategies during the pandemic.

Context: Heterotopic ossification is characterized by abnormal growth of bone in soft tissues. Neurogenic heterotopic ossification is also closely related to central nervous system injuries and has been reported to respond to radial extracorporeal shock wave therapy. Findings: In this case, a radial extracorporeal shock wave therapy (five times per week, lasted for almost one year) was applied to a patient with neurogenic heterotopic ossification on the left hip as a result of spinal cord injury. Throughout the treatment session, the heterotopic ossification lesion was gradually diminished, associated with the increase in joint range of motion, pain mitigation and decrease in serum alkaline phosphatase level. Conclusion/clinical relevance: Long-term radial extracorporeal shock wave therapy offers a promising therapeutic alternative for neurogenic heterotopic ossification.

BackgroundAlthough some advanced colorectal cancer (CRC) patients could select immunotherapy, but still most microsatellite stability (MSS) CRC patients did not respond. Our present study aims to set up a novel system for prognostic prediction and immunotherapeutic responsiveness for MSS CRC patients.MethodsUnivariable Cox regression survival analysis and least absolute shrinkage and selector operation (LASSO) regression analysis were performed to identify prognostic genes and establish immune risk signatures. Multivariate Cox regression analysis was performed to verify whether these clinical features could predict prognosis. R package was used to analyze the relationship between the immune-related risk model and these immune cells, effector molecules, and immune checkpoints.ResultsWe constructed an immune-related signature and verified its predictive capability. Immune-related signature included 12 differentially expressed IRGs (12 DE IR MSSGs), including CXCL1, CD36, FABP4, MS4A2, NRG1, VGF, GRP, HDC, XCL1, NGF, MAGEA1, and IL13. The signature consisting of 12 DE IR MSSGs was an independent and effective prognostic factor for the overall survival of CRC patients. In addition, the signature consisting of 12 DE IR MSSGs reflected the infiltration characteristics of different immunocytes in tumor immune microenvironment. The signature consisting of 12 DE IR MSSGs also had a significant correlation with immune checkpoint molecules.

Background: Pancreatic cancer (PC) is one of the most malignant cancers and its 5-year survival rate remains poor. Although immunotherapy has achieved certain therapeutic efficacy in some clinical trials, such treatment still shows low responsiveness and overall remission rate. Therefore, it is urgently necessary to dissect the tumor microenvironment and optimize the immunotherapeutic strategies against this malignancy.Methods: Using the multi-color immunohistochemistry, we investigated the expressions of B7-H3, B7-H4, HHLA2, CD8, and CD68 in 63 cases of PC tissues with the tissue microarray. Moreover, we analyzed immunolocalization features, prognostic values of this immune contexture, and clinical associations.Results: The expressions of B7-H3, B7-H4, and HHLA2 could be detected in cytokeratin (CK)+ tumor cells, CD68+macrophages, and even stromal cells. Higher expression of B7-H3 in tumor cells could predict a better survival of the PC patients. A positive correlation was found between the expressions of B7-H3 and HHLA2 in tumor cells, while there was a negative correlation between the expressions of B7-H4 and HHLA2 in tumor cells. A positive correlation was found between the expressions of B7-H3 and B7-H4 or HHLA2 in tumor-associated macrophages (TAMs), but not B7-H4 and HHLA2. Tumor-infiltrating CD8+T cells in combination with CD68+TAMs could serve as an important predictor for the postoperative prognosis of PC patients. Higher expression of B7-H3, or HHLA2 in CD68+TAMs could serve as an important predictor for poorer prognosis of PC patients. Patients with B7-H3lowB7-H4low, B7-H3lowHHLA2low, or B7-H4lowHHLA2low on CD68+TAMs could have a better postoperative prognosis compared with the other sub-populations in the combinational analysis.Conclusions: Taken together, our study indicated variable expressions and prognostic values of B7-H3, B7-H4, and HHLA2, in human PC tissues, and distinctively demonstrated that these immunosuppressive co-stimulators expressed by CD68+TAMs could be used as important bio-markers for the prognostic prediction of PC patients. Moreover, these results supported that the evaluation of these markers could be used as essential candidate targets for immunotherapy against PC.

Objective To determine the value of shear wave elastography (SWE) in assessing abdominal wall muscles, including rectus abdominis (RA), external oblique muscle (EO), internal oblique muscle, and transversus abdominis (TrA) in patients with diastasis recti abdominis (DRA) and healthy controls. Methods From October 2018 to December 2019, 36 postpartum DRA patients and 24 nulliparous healthy women were identified. Inter-rectus distance (IRD) measurements were taken by B-mode ultrasound. Shear wave speed (SWS) values were acquired by one operator at ten specific locations. Clinical and ultrasound variables, including demographics, IRD, muscle thickness, and muscle SWS, were compared between the two groups using Student’s t test or Fisher's exact test. Pearson correlation analyses were conducted for the variables of IRD, muscle thickness, and SWS in the 36 DRA patients. Results The maximum diameter of recti abdominus separation was located at the umbilicus in DRA patients (4.59 ± 1.14 cm). The SWS value was significantly lower in the RA (p = 0.003) and higher in the TrA muscle (p p p = 0.001). Conclusions The application of SWE to abdominal wall muscles in DRA patients is feasible. The correlation between SWS value and IRD in RA should be interpreted with caution.

Long non‐coding RNAs (lncRNAs) have been identified as playing critical roles in multiple diseases. However, little is known regarding their roles and mechanisms in post‐stroke angiogenesis. Our studies focused on deciphering the functional roles and the underlying mechanisms of the lncRNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) in the process of angiogenesis following oxygen‐glucose deprivation/reoxygenation (OGD/R). We characterized the up‐regulation of MALAT1 expression in the process of angiogenesis after hypoxic injury in vivo and in vitro. We further showed that compared with the empty vector, MALAT1 knockdown had significantly reduced the capacity for angiogenesis, which was measured by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium (MTT), scratching, cell cycle and immunofluorescent staining. Thus, our findings suggest that MALAT1 may mediate proangiogenic function in OGD/R. To further explore the potential mechanisms, we used lentiviruses expressing shMALAT1 and empty vector; the results revealed that shMALAT1 reduced the expression of 15‐lipoxygenase 1 (15‐LOX1), vascular endothelial growth factor (VEGF) and the phosphorylation of signal transducers and activators of transcription 3 (pSTAT3). Taken together, our results are the first to propose that MALAT1 may regulate angiogenesis through the 15‐LOX1/STAT3 signalling pathway, and they may provide a critical target for the treatment of hypoxic injury and an avenue for therapeutic angiogenesis.

Purpose The research aimed to identify the active component from Punica granatum L. to alleviate ischemia/reperfusion injury and clarify the underlying mechanism of the active component alleviating ischemia/reperfusion injury. Materials and methods The SH-SY5Y cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) was established to simulate the ischemia/reperfusion injury. According to the strategy of bioassay-guided isolation, the active component of punicalin from Punica granatum L. was identified. Flow cytometry and Western blotting were employed to evaluate the effects of OGD/R and/or punicalin on cell cycle arrest. Immunofluorescence assay was applied to assess the nucleus translocation. The relative content of ROS and GSH and the enzyme activities of CAT and SOD were examined using ELISA. Results The data of bioassay-guided isolation showed that punicalin from Punica granatum L. could alleviate OGD/R-induced cell injury in SH-SY5Y cells. Flow cytometry analysis and Western blotting for probing the expression of CDK1, p-CDK1, cyclin B1, and p21 revealed that punicalin could relieve OGD/R-induced cell cycle G0/G1 arrest. Additionally, immunofluorescence assay and Western blotting for probing the expression of TGF-β and p-Smad2/p-Smad3 showed that punicalin could relieve the OGD/R-induced TGF-β/Smad pathway. Furthermore, the TGF-β/Smad pathway inhibitor of LY2157299 was employed to confirm that the TGF-β/Smad pathway is crucial to the effect of punicalin. At last, it was indicated that punicalin could relieve OGD/R-induced oxidative stress. Conclusion Punicalin, an active component from Punica granatum L., was identified as a protective agent to alleviate the OGD/R-induced cell injury, which could exert the protective effect via TGF-β/Smad pathway-regulated oxidative stress and cell cycle arrest in SH-SY5Y cells.

Background Transmembrane 4 L six family member 5 (TM4SF5) has been found to play a vital role in the cancer process, but the relationship between TM4SF5 and colorectal cancer remains unclear. Therefore, the present study aimed to investigate the clinical and prognostic value of TM4SF5 in colorectal cancer (CRC). Methods Immunohistochemistry and RT-qPCR were used to identify the clinical significance and prognostic value of TM4SF5 expression in colon cancer. The expression of TM4SF5 was knocked down using the siRNA method to evaluate the role of TM4SF5 in regulating the biological behavior of colon cancer cell lines. Results The immunohistochemistry study revealed that the expression of TM4SF5 in human colorectal cancer tissues was significantly higher than that in adjacent normal tissues (P ). However, there was no correlation between the expression of TM4SF5 and the clinicopathological features of these patients. The RT-qPCR analysis revealed that the mRNA expression of TM4SF5 was higherin colon cancer cell lines than in normal cells (P ). The survival analysis revealed that the overall survival (OS) rate of patients with a low expression of TM4SF5 was significantly higher, when compared to patients with a high expression of TM4SF5 (P = 0.048). The COX model revealed that the expression of TM4SF5 (P ) and clinical stage (P = 0.025) can be used as independent prognostic factors for patients with colon cancer. In addition, the knockdown of TM4SF5 in colon cancer cell lines LoVo, SW480, RKO and HCT-116 significantly reduced the ability of cells (such as proliferation, migration and invasion). Conclusion The present results indicate that the increase in TM4SF5 expression in human colon cancer is associated with cancer progression and poor survival, and that its intervention can be an important therapeutic strategy against colon cancer.

Purpose. The research aimed to identify the active component from Punica granatum L. to alleviate ischemia/reperfusion injury and clarify the underlying mechanism of the active component alleviating ischemia/reperfusion injury. Materials and Methods. The SH-SY5Y cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) was established to simulate the ischemia/reperfusion injury. According to the strategy of bioassay-guided isolation, the active component of punicalin from Punica granatum L. was identified. Flow cytometry and Western blotting were employed to evaluate the effects of OGD/R and/or punicalin on cell cycle arrest. Immunofluorescence assay was applied to assess the nucleus translocation. The relative content of ROS and GSH and the enzyme activities of CAT and SOD were examined using ELISA. Results. The data of bioassay-guided isolation showed that punicalin from Punica granatum L. could alleviate OGD/R-induced cell injury in SH-SY5Y cells. Flow cytometry analysis and Western blotting for probing the expression of CDK1, p-CDK1, cyclin B1, and p21 revealed that punicalin could relieve OGD/R-induced cell cycle G0/G1 arrest. Additionally, immunofluorescence assay and Western blotting for probing the expression of TGF-β and p-Smad2/p-Smad3 showed that punicalin could relieve the OGD/R-induced TGF-β/Smad pathway. Furthermore, the TGF-β/Smad pathway inhibitor of LY2157299 was employed to confirm that the TGF-β/Smad pathway is crucial to the effect of punicalin. At last, it was indicated that punicalin could relieve OGD/R-induced oxidative stress. Conclusion. Punicalin, an active component from Punica granatum L., was identified as a protective agent to alleviate the OGD/R-induced cell injury, which could exert the protective effect via TGF-β/Smad pathway-regulated oxidative stress and cell cycle arrest in SH-SY5Y cells.

AimThe aim of the study is to investigate a variation in the gene SLC6A19 in a female patient with Hartnup disorder manifested only by seizure.MethodsDNA samples collected from the patient and her parents were analyzed and twelve exons of the SLC6A19 gene were amplified and sequenced.ResultsWe found c.47C>T and c.1522G>A mutations in the gene SLC6A19 belonging to the patient, which are missense mutations inherited from her parents. The c.47C>T mutation is from her father and c.1522G>A is inherited from her mother. The parents are both heterozygous healthy carriers.ConclusionTwo novel mutations of the SLC6A19 gene are revealed in the female patient with Hartnup disorder, exhibiting no typical dermatologic problems, but having dramatic neurological symptoms.

Subarachnoid hemorrhage (SAH) is a severe neurological disease, which is associated with a significant number of cases of premature mortality and disability worldwide. Mild hypothermia (MH) has been proposed as a potential therapeutic strategy to reduce neuronal injury following SAH. The present study aimed to investigate the mechanisms of MH's protective role in the process of SAH. The present study demonstrated that MH was able to protect against early brain injury in a rat model of SAH. Treating SAH rats with MH reduced the release of reactive oxygen species and prevented activation of apoptotic cascades. Furthermore, the protective effects of MH were shown to be mediated by enhanced activity of the tropomyosin receptor kinase B/extracellular signal‑regulated kinases/cAMP response element binding protein (TrkB/ERK/CREB) pathway. Inhibition of TrkB/ERK/CREB activity using a small molecule inhibitor largely abolished the beneficial effects of MH in SAH rats. These results outline an endogenous mechanism underlying the neuroprotective effects of MH in SAH.

Our own study as well as others have previously reported that hypoxia activates 15-lipoxygenase (15-LO) in the brain, causing a series of chain reactions, which exacerbates ischemic stroke. 15-hydroxyeicosatetraenoic acid (15-HETE) and 15-oxo-eicosatetraenoic acid (15-oxo-ETE/15-KETE) are 15-LO-specific metabolites of arachidonic acid (AA). 15-HETE was found to be rapidly converted into 15-oxo-ETE by 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in some circumstances. We have demonstrated that 15-HETE promotes cerebral vasoconstriction during hypoxia. However, the effect of 15-oxo-ETE upon the contraction of cerebral vasculature remains unclear. To investigate this effect and to clarify the underlying mechanism, we performed immunohistochemistry and Western blot to test the expression of 15-PGDH in rat cerebral tissue, examined internal carotid artery (ICA) tension in isolated rat ICA rings. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to analyze the expression of voltage-gated potassium (Kv) channels (Kv2.1, Kv1.5, and Kv1.1) in cultured cerebral arterial smooth muscle cells (CASMCs). The results showed that the levels of 15-PGDH expression were drastically elevated in the cerebral of rats with hypoxia, and 15-oxo-ETE enhanced ICA contraction in a dose-dependent manner. This effect was more significant in the hypoxic rats than in the normoxic rats. We also found that 15-oxo-ETE significantly attenuated the expression of Kv2.1 and Kv1.5, but not Kv1.1. In conclusion, these results suggest that 15-oxo-ETE leads to the contraction of the ICA, especially under hypoxic conditions and that specific Kv channels may play an important role in 15-oxo-ETE-induced ICA constriction.

Background/aims With advances in RNA-sequencing (RNA-seq), exploring the expression and transcripts of different classes of genes are now possible. Our purpose was to analyse to the long non-coding RNAs (lncRNAs) in mouse brain microvascular endothelial cells (bEnd.3) after oxygen-glucose deprivation/re-oxygenation (OGD/R). Methods RNA-seq was employed to explore the expression of lncRNAs, and quantitative real-time PCR (qRT-PCR) was used to identify the results of RNA-seq. Furthermore, the biological functions of the lncRNAs were identified by cell viability, wound healing, transwell, tube formation and immunofluorescent staining assays. Finally, the molecular mechanisms involving the differentially expressed lncRNAs were further explored by bioinformatics and Western blotting (WB). Results In total, 2710 lncRNAs were found, 33 of which were significantly differentially expressed, with 18 upregulated lncRNAs and 15 downregulated lncRNAs in brain microvascular endothelial cells following OGD/R. Among the dysregulated genes, G protein-coupled receptor 137b-pseudogene (Gpr137b-ps), predicted gene 32856 (Gm32856), small nucleolar RNA host gene 17 (snhg17), chaperonin containing Tcp1 and subunit 6a (Cct6a) were significantly upregulated lncRNAs; this finding was further validated using qRT-PCR. Moreover, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes (KEGG) pathway analyses were employed to decipher the potential target genes and signaling pathways of the differentially expressed lncRNAs. Finally, we selected pseudogene-expressed lncRNA Gpr137b-ps as a candidate gene, and report for the first time that pseudogenes can mediate angiogenesis and their potential target genes, namely, 15-lipoxygenase1 (15-LOX1), Signal Transducer and Activator of Transcription 3 (S TAT3) and vascular endothelial growth factor (VEGF). Conclusion Therefore, our study revealed that Gpr137b-ps plays critical roles in the process of angiogenesis, suggesting avenues for the development of future therapeutic strategies that contribute to promoting angiogenesis following I/R.

In recent years, accumulating evidence has revealed that microRNAs play critical roles in ischemia stroke. This study was designed to investigate the expression level and effects of microRNA (miR)-186-5p on ischemia stroke, and its underlying molecular mechanism. Firstly, we demonstrated that miR-186-5p were significantly up-regulated and induced apoptosis in oxygen and glucose deprivation/reperfusion (OGD/R) model. Moreover, we found that miR-186-5p reduced the expression of insulin-like growth factor (IGF)-1, an essential factor for the development of the nervous system. Meanwhile, miR-186-5p inhibitor enhanced cell viability and IGF-1 expression. Furthermore, IGF-1 was confirmed as a direct target gene of miR-186-5p by luciferase activity assay. In addition, miR-186-5p was upregulated in ischemia stroke patients' serum compared with healthy donors. These data demonstrated that miR-186-5p was an adverse factor by inducing neuron apoptosis and suppressing IGF-1 in ischemia stroke model, and suggested that miR-186-5p may be a diagnostic marker and potential therapeutic target for ischemia stroke patients.

Aim The aim of the study is to investigate a variation in the gene SLC6A19 in a female patient with Hartnup disorder manifested only by seizure. Methods DNA samples collected from the patient and her parents were analyzed and twelve exons of the SLC6A19 gene were amplified and sequenced. Results We found c.47C>T and c.1522G>A mutations in the gene SLC6A19 belonging to the patient, which are missense mutations inherited from her parents. The c.47C>T mutation is from her father and c.1522G>A is inherited from her mother. The parents are both heterozygous healthy carriers. Conclusion Two novel mutations of the SLC6A19 gene are revealed in the female patient with Hartnup disorder, exhibiting no typical dermatologic problems, but having dramatic neurological symptoms.

As a component of the neurovascular unit, cerebral smooth muscle cells (CSMCs) are an important mediator in the development of cerebral vascular diseases such as stroke. Epoxyeicosatrienoic acids (EETs) are the products of arachidonic acid catalyzed by cytochrome P450 epoxygenase. EETs are shown to exert neuroprotective effects. In this article, the role of EET in the growth and apoptosis of CSMCs and the underlying mechanisms under oxygen glucose deprivation (OGD) conditions were addressed. The viability of CMSCs was decreased significantly in the OGD group, while different subtypes of EETs, especially 14,15-EET, could increase the viability of CSMCs under OGD conditions. RAPA (serine/threonine kinase Mammalian Target of Rapamycin), a specific mTOR inhibitor, could elevate the level of oxygen free radicals in CSMCs as well as the anti-apoptotic effects of 14,15-EET under OGD conditions. However, SP600125, a specific JNK (c-Jun N-terminal protein kinase) pathway inhibitor, could attenuate oxygen free radicals levels in CSMCs as well as the anti-apoptotic effects of 14,15-EET under OGD conditions. These results strongly suggest that EETs exert protective functions during the growth and apoptosis of CSMCs, via the JNK/c-Jun and mTOR signaling pathways in vitro. We are the first to disclose the beneficial roles and underlying mechanism of 14,15-EET in CSMC under OGD conditions.

This study sought to clarify the effects of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in angiogenesis and neurological functional recovery after cerebral ischaemic stroke in mice. In vivo, we performed behavioural tests to determine functional recovery after stroke. Double immunofluorescence staining of CD31 and Ki67/PCNA was performed to evaluate the effects of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid on angiogenesis in an MCAO mouse model. In vitro, we investigated the effects of 15-hydroxyeicosatetraenoic acid on BMVEC proliferation and migration. Our results show that MCAO upregulates 15-lipoxygenase expression in a time-dependent manner, especially in later stages of post-stroke. We confirmed that cerebral infarct area was reduced and neurological dysfunction was gradually attenuated after stroke, while 12/15-lipoxygenase knockout mice exhibited the opposite effects. Furthermore, immunofluorescence studies revealed 15-lipoxygenase increased the proliferation of mouse brain vascular endothelial cells in a time-dependent manner, while 12/15-lipoxygenase knockout blocked these effects. Moreover, 15-hydroxyeicosatetraenoic acid promoted proliferation and tube formation in BMVECs. These results demonstrate positive influence of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in angiogenesis and neuronal recovery after ischaemic stroke in mice. We also confirmed the PI3K/Akt signalling pathway was necessary for the effects of 15-hydroxyeicosatetraenoic acid in regulation of BMVEC proliferation and migration, which may potentially be a novel target for the recovery from ischaemic stroke.

Fangliang Yang,1,2 Yuan Li,1 Lingyun Xu,1 Yulan Zhu,1 Haiyan Gao,1 Lin Zhen,1 Lin Fang2 1Department of Thyroid and Breast Surgery, Changzhou No 2 People’s Hospital Affiliated to Nanjing Medical University, Changzhou, 2Department of Thyroid and Breast Surgery, Shanghai No 10 People’s Hospital, Clinical College of Nanjing Medical University, Shanghai, People’s Republic of China Background: MicroRNAs (miRNAs) have been shown to be involved in the initiation and progression of cancers in the literature. In this study, we aimed to evaluate the clinicopathological role of miR-17 in breast cancer. Materials and methods: The expression of miR-17 was measured in 132 breast cancer tissues and paired adjacent normal tissues by using real-time quantitative polymerase chain reaction. The association between miR-17 expression levels and clinicopathological parameters was also analyzed. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assays were used to investigate the role of miR-17 in the regulation of breast cancer cells. Results: The expression of miR-17 was remarkably increased in breast cancer tissues and cell lines. Clinical association analysis revealed that a high expression of miR-17 was prominently associated with poor survival time in breast cancer. Overexpression of miR-17 promoted cell proliferation and induced tumor growth. Conclusion: Our findings clarified that the upregulation of miR-17 played a vital role in breast cancer progression and suggested that miR-17 could be used as a prognostic biomarker for breast cancer. Keywords: miR-17, breast cancer, biomarker, cell proliferation

Neural stem cells are able to self-renew and generate glial and neuronal lineages. Neural stem cell may serve as therapeutic method for neurological disorders including spinal cord injuries, Parkinson’s disease, Huntington’s disease and Alzheimer’s disease. Long noncoding RNAs (lncRNAs) are longer than 200 nucleotides with limited protein-coding capacity. Recent studies have demonstreated that lncRNAs play an important role in several cellular processes including cell differentiation, cell development, proliferation, apoptosis, invasion and migration. However, the role of lncRNA human urothelial carcinoma associated 1 (UCA1) in the development of neural stem cells remains unknown. In this study, we showed that the expression of UCA1 was upregulated in the neural stem cell in a time-dependent manner. Knockdown of UCA1 suppressed the neural stem cell proliferation. Inhibition of UCA1 decreased the expression of nestin and the formation of neurosphere. Moreover, knockdown of UCA1 suppressed the neural stem cell differentiation to astrocyte and promoted the neural stem cell differentiation to neuron. Furthermore, we demonstrated that knockdown of UCA1 increased the expression of miR-1 in the neural stem cell and suppressed the expresion of Hes1, which is one target gene of miR-1. In addition, ectopic expression of Hes1 could impair siUCA1-induced neural stem cells proliferation. Overexpression of Hes1 suppressed siUCA1-induced β-tubulin expression and promoted siUCA1-inhibited GFAP expression in the neural stem cell. These results suggested that UCA1 regulated the neural stem cell proliferation and differentiation through regulating Hes1 expression.

OBJECTIVE To examine whether obesity/overweight is a risk predictor for breast cancer recurrence and death by menopausal status in a retrospective study. METHODS We performed a retrospective analysis of 1017 breast cancer patients treated in our hospital from January 2004 to December 2012. Three groups were divided according to body mass index (BMI) when breast cancer diagnosis: normal weight, BMI

The core–shell Al/Co nanocomposites with sheet-like and spherical Co nanocrystals as shells were fabricated via a displacement reaction between Al and CoCl2·6H2O in a glycol solution by the controlling feeding rate of NH4F glycol solution. By eroding the Al core in HCl aquatic solution, hollow spherical nanostructures assembled by sheet-like and spherical Co nanocrystals were obtained. The possible mechanism for the formation of Co hollow nanostructures composed of different shaped nanocrystals has been discussed.

Objective: 5-lipoxygenase-activating protein gene (ALOX5AP) has been recognized as a susceptibility gene for stroke. In this work, we explored the association of 6 ALOX5AP SNPs with cerebral infarction (CI) in a northeastern Chinese Han population, using a case-control design. Methods: A group of patients with cerebral infarction were randomly chosen as case group in northeastern Chinese Han population. Another comparative group of individuals without stroke were chosen as the control group. By utilizing TaqMan probe based real-time fluorescent PCR and DNA sequencing method, this study focused on 6 SNPs of ALOX5AP gene and analyzed the association with the hereditary susceptibility of cerebral infarction. Results: We found that, the rs9579646 G allele frequency was significantly associated with higher ischemic cerebral infarction. There was no significant difference of rs9551963, rs9315050, rs4769874, rs10507391 and rs4147064 genotype frequencies between the case and control group. Haplotype-based association analysis of the block involving rs9579646 and rs10507391 revealed that the increased risk of stroke was significantly associated with haplotype GT and GA. Conclusion: These results suggested that the genetic variants in ALOX5AP might be related to the risk of stroke in northeastern Chinese Han population. The SNP rs9579646 may be a diagnostic index of cerebral infarction.

Background and Purpose— We aimed to develop a risk score (intracerebral hemorrhage–associated pneumonia score, ICH-APS) for predicting hospital-acquired stroke-associated pneumonia (SAP) after ICH. Methods— The ICH-APS was developed based on the China National Stroke Registry (CNSR), in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. Variables routinely collected at presentation were used for predicting SAP after ICH. For testing the added value of hematoma volume measure, we separately developed 2 models with (ICH-APS-B) and without (ICH-APS-A) hematoma volume included. Multivariable logistic regression was performed to identify independent predictors. The area under the receiver operating characteristic curve (AUROC), Hosmer–Lemeshow goodness-of-fit test, and integrated discrimination index were used to assess model discrimination, calibration, and reclassification, respectively. Results— The SAP was 16.4% and 17.7% in the overall derivation (n=2998) and validation (n=2000) cohorts, respectively. A 23-point ICH-APS-A was developed based on a set of predictors and showed good discrimination in the overall derivation (AUROC, 0.75; 95% confidence interval, 0.72–0.77) and validation (AUROC, 0.76; 95% confidence interval, 0.71–0.79) cohorts. The ICH-APS-A was more sensitive for patients with length of stay >48 hours (AUROC, 0.78; 95% confidence interval, 0.75–0.81) than those with length of stay P =0.20) and validation ( P =0.66) cohorts. Similarly, a 26-point ICH-APS-B was established. The ICH-APS-A and ICH-APS-B were not significantly different in discrimination and reclassification for SAP after ICH. Conclusion— The ICH-APSs are valid risk scores for predicting SAP after ICH, especially for patients with length of stay >48 hours.

Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease leading to recurrent ischemic stroke and vascular dementia. Numerous mutations in the 23 exons of the NOTCH3 gene have been reported to cause CADASIL in Caucasian populations, but the full spectrum of genetic changes leading to this disease is yet to be known and, especially, very few reports are available on CADASIL in Asian populations. Methods and Results We genotyped members of a 5-generational Han Chinese family with CADASIL patients and identified an R133C mutation in the NOTCH3 gene. Clinical analysis demonstrated that the penetrance of the mutation was not complete. Five of the mutation carriers, not exposed to the known vascular risk factors, did not show any clinical feature of CADASIL, suggesting the importance of environmental factors to the development of this disease. Conclusions Members of a 5-generational Han Chinese family with CADASIL patients had an R133C mutation in the NOTCH3 gene but only individuals exposed to known vascular risk factors developed CADASIL.

Severe hypoxia induces the constriction of internal carotid arteries (ICA), which worsens ischemic stroke in the brain. A few metabolites are presumably involved in hypoxic vasoconstriction, however, less is known about how such molecules provoke this vasoconstriction. We have investigated the influence of 15-hydroxyeicosatetrienoic acid (15-HETE) produced by 15-lipoxygenase (15-LOX) on vasoconstriction during hypoxia. As showed in our results, 15-LOX level increases in ICA endothelia and smooth muscles. 15-HETE enhances the tension of ICA ring in a dose-dependent manner, as well as attenuates the activities and expression of voltage-gated potassium channels (Kv 1.5 and Kv 2.1). Therefore, the down-regulation of Kv channels by 15-HETE during hypoxia may weaken the repolarization of action potentials and causes a dominant influx of calcium ions to enhance smooth muscle tension and ICA constriction.