Exploring stroke risk and prevention in China: insights from an outlier.

In contrast to the declining trend in most regions worldwide, the incidence of stroke is increasing in China and is leading to an alarming burden for the national healthcare system. In this review, we have generated new insights from this outlier, and we aim to provide new information that will help decrease the global stroke burden, especially in China and other regions sharing similar problems with China. First of all, several unsolved aspects fundamentally accounting for this discrepancy were promising, including the serious situation of hypertension management, underdiagnosis of atrial fibrillation and underuse of anticoagulants, and unhealthy lifestyles (e.g., heavy smoking). In addition, efforts for further alleviating the incidence of stroke were recommended in certain fields, including targeted antiplatelet regimes and protections from cold wave-related stroke. Furthermore, advanced knowledge about cancer-related strokes, recurrent strokes and the status preceding stroke onset that we called stroke-prone status herein, is required to properly mitigate patient stroke risk, and to provide improved outcomes for patients after a stroke has occurred.

Klippel-Trenaunay and Sturge-Weber Overlap Syndrome with KRAS and GNAQ mutations.

Patients with combined phenotypes of Sturge-Weber syndrome and Klippel-Trenaunay syndrome have been reported, though the underlying genetic spectrum in these individuals remains to be elucidated. We reported the patient presenting with Klippel-Trenaunay and Sturge-Weber overlap syndrome in mainland China. Histopathologic study confirmed the hemangioma of vein and capillary. Co-existence of a novel somatic KRAS c.182_183 delins TC mutation and GNAQ c.548G>A mutation was identified in the affected skin tissue rather than paired peripheral blood. The somatic mutations of GNAQ and KRAS may affect MAPK-ERK signaling pathway, resulting in endothelial anomaly and blood vessel malformation.

Analysis of postpartum reversible cerebral vasoconstriction syndrome in China: A case report and literature review.

Reversible cerebral vasoconstriction syndrome (RCVS) is a rare clinical syndrome accompanying with severe headache as its main symptom. Postpartum reversible cerebral vasoconstriction syndrome (PPRCVS) refers to RCVS occurring in the puerperium, in which it has a low incidence, and that is easily missed diagnosed and misdiagnosed in clinical practice.By searching in CNKI and Wanfang databases, 9 published articles reported PPRCVS were found, totally including 12 cases with PPRCVS. The clinical data of these 12 cases were accordingly analyzed and summarized. The characteristics of these cases were compared with those reported in other countries, and eventually the clinical characteristics of Chinese PPRCVS patients were summarized.The clinical characteristics of Chinese PPRCVS patients were basically as same as those found in other countries, while the onset age was earlier, PPRCVS often occurred earlier after delivery, with higher proportions of concomitant symptoms and abnormal laboratory and imaging examinations; moreover, and fewer patients were diagnosed by digital subtraction angiography (DSA).

Association of Cerebral Arterial Stiffness with Initial Severity in Acute Ischemic Stroke.

AIM: To evaluate the association between cerebral arterial stiffness, measured using carotid-cerebral pulse wave velocity (ccPWV), and the initial severity estimated by the National Institutes of Health Stroke Scale (NIHSS) after acute ischemic stroke (AIS). METHODS: We prospectively studied 402 consecutive patients with first-ever acute cerebral infarction who underwent brain multimodal magnetic resonance, ccPWV, echocardiography, and carotid ultrasonography during the admission period. Their stroke subtypes were classified using the Trial of Org 10172 in Acute Stroke Treatment classification. Severe initial stroke severity was defined as an NIHSS score ＞6 on admission. RESULTS: We observed that 168 (41.79%) patients had severe initial stroke severity. A multivariate logistic regression analysis revealed that ccPWV [as a continuous variable; odds ratios (OR) (95% confidence intervals (CI)): 1.36 (1.08-1.72); P=0.010] and ccPWV ＞6.87 m/s [OR (95% CI): 8.13 (3.06-21.58); P＜0.001], calculated from the receiver-operating characteristic curve, remained independent determinants of severe initial stroke severity in three models. Furthermore, we observed that ccPWV significantly correlated with the NIHSS score, and the value of ccPWV was most strongly correlated with the NIHSS score (r=0.82, P＜0.001) in subjects with small vessel occlusion (SVO) among all stroke subtypes. CONCLUSIONS: Cerebral arterial stiffness was independently associated with initial severity in AIS patients, and may be more strongly correlated with the initial SVO severity than those of other subtypes.

Cerebral Arterial Stiffness as A New Marker of Early Stage Atherosclerosis of The Cerebral Large Artery in Acute Stroke.

AIM: Carotid-cerebral pulse wave velocity (ccPWV) reflects the segment (C-M segment) stiffness between the common carotid artery and ipsilateral middle cerebral artery. C-M segment atherosclerosis (CMSA) is regarded the most frequent cause of anterior circulation ischemic stroke. We aimed to evaluate the association of ccPWV with early stage CMSA in this study. METHODS: Eighty-one acute ischemic stroke (AIS) patients with 154 C-M segments who were successfully evaluated with digital subtraction angiography, ccPWV, carotid intima-media thickness (cIMT), and brachial-ankle pulse wave velocity were enrolled into this study. Patient demographics and clinical data were retrieved from our AIS databases. RESULTS: Multivariate analyses showed that CMSA was independently associated with higher systolic BP, ccPWV, and cIMT. ccPWV and cIMT presented good diagnostic values for evaluating early stage CMSA in the receiver operating characteristic curve analyses. The areas under the curve (AUCs) of ccPWV were significantly higher than that of cIMT (Z=2.204, P=0.007). The AUC, sensitivity, specificity, Youden index, and cutoff of ccPWV for detecting early stage CMSA were 0.815 (P＜0.001), 86%, 70.7%, 0.567, and 5.4 m/s, respectively. Furthermore, ccPWV was significantly correlated with the stenosis of CMSA at the early stage in Spearman's correlation analyses (r=0.877, P＜0.001) and fractional polynomial plot with 95% confidence intervals. CONCLUSIONS: Cerebral arterial stiffness has the potential to be a new marker of early stage atherosclerosis of the cerebral large artery. This finding may help us prevent the occurrence of stroke and decrease the burden of society from stroke patients.

Vagus Nerve Stimulation Attenuates Cerebral Microinfarct and Colitis-induced Cerebral Microinfarct Aggravation in Mice.

Cerebral cortical microinfarct (CMI) is common in patients with dementia and cognitive decline. Emerging studies reported that intestinal dysfunction influenced the outcome of ischemic stroke and that vagus nerve stimulation (VNS) protected against ischemic stroke. However, the effects of intestinal dysfunction and VNS on CMI are not clear. Therefore, we examined the influence of colitis and VNS on CMI and the mechanisms of VNS attenuating CMI in mice with colitis. CMI was induced using a two-photon laser. Colitis was induced using oral dextran sodium sulfate (DSS). The cervical vagus nerve was stimulated using a constant current. In vivo blood-brain barrier (BBB) permeability was evaluated using two-photon imaging. Infarct volume, microglial and astrocyte activation, oxidative stress and proinflammatory cytokine levels were assessed using immunofluorescent and immunohistochemical staining. The BBB permeability, infarct volume, activation of microglia and astrocytes and oxidative stress increased significantly in mice with colitis and CMI compared to those in mice with CMI. However, these processes were reduced in CMI mice when VNS was performed. Brain lesions in mice with colitis and CMI were significantly ameliorated when VNS was performed during the acute phase of colitis. Our study demonstrated that VNS alleviated CMI and this neuroprotection was associated with the suppression of BBB permeability, neuroinflammation and oxidative stress. Also, our results indicated that VNS reduced colitis-induced microstroke aggravation.

Association between Cerebral Arterial Stiffness and Large Artery Atherosclerosis in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Carotid-cerebral pulse wave velocity (ccPWV) reflects the segment (C-M segment) stiffness between common carotid artery and ipsilateral middle cerebral artery. The C-M segment atherosclerosis (CMSA) is regarded as a most frequent cause of anterior circulation ischemic stroke. We therefore, attempted to investigate the relationship between cerebral arterial stiffness and CMSA, and provide reliable data for the early diagnosis of CMSA. METHODS: Between June 2012 and August 2016, 81 acute ischemic stroke (AIS) patients with 154 C-M segments successfully evaluated with digital subtraction angiography and ccPWV were enrolled into this study. Patient demographics and clinical data were retrieved from our AIS databases. RESULTS: Multivariate analyses showed that ccPWV was independently associated with CMSA (ß = 39.6, P = .009) and Systolic blood pressure (ß = 7.1, P < .001) in AIS patients. The values of ccPWV had a trend to be higher in the groups with more lesions (F = 45.9, P < .01) and severer stenosis (F = 102.6, P = .000), and was positively correlated with the number of lesions (r = .662, P = .000), and degree of stenosis (r = .858, P = .000) of CMSA. The fractional polynomial plots with 95% CIs also describe the close relationship between ccPWV and the number of lesions and degree of stenosis in CMSA. CONCLUSIONS: Cerebral arterial stiffness is independently associated with the presence of CMSA, closely related to the vascular damage of C-M segment and reflects the vascular structure change of C-M segment in AIS patients. It may have the potential for assessment of CMSA in its initial stage.

Ischemic stroke damages the intestinal mucosa and induces alteration of the intestinal lymphocytes and CCL19 mRNA in rats.

The immunoreaction has a pivotal effect on ischemic stroke. It has been demonstrated that intestinal lymphocytes infiltrate into the brain and aggravate tissue injury after stroke. However, less attention has been paid to the influence on the intestinal immunology as well as morphology. Here, we utilized a rat permanent middle cerebral artery occlusion (MCAO) model to investigate the influences on intestinal mucosa, lymphocytes of the gut-associated lymphoid tissue (GALT), and the intestinal expression of CCL25 mRNA and CCL19 mRNA of stroke. Rats were randomly divided into stroke, sham, and control groups. Stroke and sham groups were further divided into interval groups of 6h, 12h, and 24h after surgery. Intestinal pathophysiological changes were observed by hematoxylin-eosin (H&E) staining. The lymphocyte numbers were detected by flow cytometry. The expression of CCL25 mRNA and CCL19 mRNA was tested with the PCR technique. We found significant necrosis and shedding of the epithelium after stroke. Moreover, the lesion aggravated with time. In addition, there was a significant increase of T lymphocytes in Peyer's patches (PPs), especially at 12h and 24h after stroke, while no differences in the number of B lymphocytes and the intraepithelial lymphocytes (IELs) were found. The data displayed no alteration of CCL25 mRNA expression. In contrast, an upregulation of CCL19 mRNA expression was detected at 6h after stroke. This study showed that ischemic stroke significantly damaged the intestinal epithelium and activated intestinal immunity.

Intravenous PEP-1-GDNF is protective after focal cerebral ischemia in rats.

Glial cell line-derived neurotrophic factor (GDNF) is a potential therapeutic protein on a variety of central nervous system diseases including ischemic stroke. However, GDNF is a large molecule that cannot cross the blood-brain barrier (BBB), which is still intact in the early hours after stroke when neural rescue is possible. PEP-1 protein transduction domain can deliver protein cargo across the cell membrane and the BBB. In the present study, we generated a novel fusion protein PEP-1-GDNF and examined whether PEP-1-GDNF is protective in focal cerebral ischemia. PEP-1-GDNF (200 µg/kg) or PBS was intravenously applied over 5 min immediately after reperfusion of 90 min transient middle cerebral artery occlusion (MCAO). After 28 days, rats were deeply anesthetized and decapitated. Behavioral tests were performed during this period. The results showed that PEP-1-GDNF significantly reduced the infarct volume and improved behavioral function. Further, PEP-1-GDNF promoted the cell proliferation and differentiation in the dentate gyrus of the hippocampus and attenuated ischemia-induced learning and memory damage.

[Effects of thymectomy on bone age and height development in juvenile myasthenia gravis].

OBJECTIVE: To explore the effects of clinical indicators, particularly thymectomy on the development of juvenile myasthenia gravis (JMG) through the developmental status of bone age (BA) and height. METHODS: A cross-sectional study of 80 JMG patients was recruited to examine whether JMG patients had the abnormalities of height and bone development according to the distribution of height standard deviation score (Ht SDS) and BA. RESULTS: The mean BA was delayed by (0.15 ± 1.32) years compared with patient chronological age (CA). The mean Ht SDS (HtCA SDS -1.25 ± 1.03) was also lower than healthy controls. In multivariate analysis, the age at onset was negatively associated with delayed BA (P=0.007) whereas the cumulative intake of prednisone was negatively associated with HtCA SDS (P=0.043). No significant correlation existed between thymectomy and delayed BA or HtCA SDS. Delayed BA and slow growth existed in JMG patients. The age at onset of JMG was a correlative factor for delayed BA. And the intake of cumulative prednisone might be a determinant of height retardation. Thymectomy had no impact on the development of bone and height. CONCLUSION: We should pay more attention to monitoring BA and height in JMG patients to take appropriate therapeutic interventions.

Spontaneous white matter lesion in brain of stroke-prone renovascular hypertensive rats: a study from MRI, pathology and behavior.

Hypertension is considered one of the most important controllable risk factors for white matter lesion (WML). Our previous work found that stroke-prone renovascular hypertensive rats (RHRSP) displayed a high rate of WML. This study aimed to investigate the WML in RHRSP from MRI, pathology and behavior. RHRSP model was established by two-kidney, two-clipmethod and kept for 20 weeks. WML was decteted by magnetic resonance imaging (MRI) and loyez staining. Cognition was tested by morris water maze (MWM). Vascular changes were observed by HE staining on brain and carotid sections. Ultrastucture of blood brain barrier (BBB) were observed by transmission electron microscope. Immunofluorescence was used to detect albumin leakage and cell proliferation. T(2)-weighted MRI scans of RHRSP displayed diffuse, confluent white-matter hyperintensities. Pathological examination of the same rat showed marked vacuoles, disappearence of myelin and nerve fibers in white matter, supporting the neuroimaging findings. Spatial learning and memory impairment were observed in RHRSP. The small arteries in brain exhibited fibrinoid necrosis, hyalinosis and vascular remodeling. BBB disruption and plasma albumin leakage into vascular wall was observed in RHRSP. Increased cell proliferation in subventricular zone was seen in RHRSP. RHRSP demonstrated spontaneous WML and cognitive impairment. Hypertensive small vessel lesions and BBB disruption might paly causative factors for the onset and development of WML. The characteristic features of WML in RHRSP suggested it a valid animal model for WML.

Beclin 1 knockdown retards re-endothelialization and exacerbates neointimal formation via a crosstalk between autophagy and apoptosis.

OBJECTIVE: Endothelial regeneration is an essential process for the prevention of excessive neointimal formation following endothelial denudation. Beclin 1, a mammalian autophagy gene, is a link between autophagy and apoptosis. We hypothesized that the interference of Beclin 1 can influence re-endothelialization and ultimately affect neointimal formation by regulating autophagy and apoptosis. METHODS: A rat carotid injury model of endothelial denudation was used, and small interfering RNA of Beclin 1 was perivascularly administered. Neointima was evaluated by morphological analysis. von Willebrand factor, Beclin 1, LC3, autophagic substrate p62 and caspase-3 levels were detected by immunofluorescence or Western blotting. Terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling assay was performed to evaluate apoptosis. RESULTS: Carotid injury induced an upregulation of Beclin 1 protein which was down regulated by more than 50% with small RNA interference. Beclin 1 knockdown significantly retarded re-endothelialization 7 days after injury and subsequently augmented neointima by more than 2 folds at 14 and 21 days. Autophagy and apoptosis were detected to reveal the regulatory effect of Beclin 1. The injury-activated autophagy, shown by the increased levels of punctate LC3 and LC3II as well as decreased p62 expression, was significantly inhibited by Beclin 1 knockdown. Meanwhile, the apoptotic endothelial cell number was increased and caspase-3 was up-regulated, though the expression of truncated BID was not significantly influenced. CONCLUSION: Beclin 1 knockdown exacerbated neointimal formation after rat carotid injury, associated with retarded re-endothelialization due to enhanced apoptosis, while simultaneously prohibiting autophagic activation. The data suggested an essential role of Beclin 1 as a regulator between autophagy and apoptosis in the setting of neointimal formation.

Exogenous fractalkine enhances proliferation of endothelial cells, promotes migration of endothelial progenitor cells and improves neurological deficits in a rat model of ischemic stroke.

Fractalkine/CX3CL1, also called neurotactin, has been described as an angiogenic agent, and its expression is up-regulated in the penumbra after ischemia. This study was conducted to investigate the neovascular potential of fractalkine on rat models of transient middle cerebral artery occlusion (MCAO). Rats receiving intracerebroventricular injections of fractalkine were found to have improved neurological deficits, reduced cerebral infarct size and increased neuron survival for both doses (100ng and 1µg). Fractalkine exerted angiogenic effects that showed dose-dependent higher vascular densities in the peri-infarct area. Furthermore, exogenous fractalkine increased the proliferation of endothelial cells in a dose-dependent manner and enhanced the migration of endothelial progenitor cells at the higher dose (1µg) in ischemic penumbra. In conclusion, intracerebroventricular administration of fractalkine reduces ischemic damage by promoting neuroprotection and by inducing endothelial cell proliferation and endothelial progenitor cell migration, thereby enhancing neovascularization in the peri-infarct region.

Scutellarin attenuates hypertension-induced expression of brain Toll-like receptor 4/nuclear factor kappa B.

Hypertension is associated with low-grade inflammation, and Toll-like receptor 4 (TLR4) has been shown to be linked to the development and maintenance of hypertension. This study aimed to investigate the effects of scutellarin (administered by oral gavage daily for 2 weeks) on brain TLR4/nuclear factor kappa B-(NF- κ B-) mediated inflammation and blood pressure in renovascular hypertensive (using the 2-kidney, 2-clip method) rats. Immunofluorescence and western immunoblot analyses revealed that hypertension contributed to the activation of TLR4 and NF- κ B, accompanied by significantly enhanced expression of proinflammatory mediators, such as tumor necrosis factor- α (TNF- α ), interleukin-1 ß (IL-1 ß ), and interleukin-18 (IL-18). Furthermore, expression of the antiapoptotic protein, myeloid cell leukemia-1 (Mcl1), was decreased, and the pro-apoptotic proteins, Bax and cleavedcaspase-3 p17 were increased in combined cerebral cortical/striatal soluble lysates. Scutellarin significantly lowered blood pressure and attenuated the number of activated microglia and macrophages in brains of hypertensive rats. Furthermore, scutellarin significantly reduced the expression of TLR4, NF- κ B p65, TNF- α , IL-1 ß , IL-18, Bax and cleaved-caspase-3 p17, and increased the expression of Mcl1. Overall, these results revealed that scutellarin exhibits anti-inflammatory and anti-apoptotic properties and decreases blood pressure in hypertensive rats. Therefore, scutellarin may be a potential therapeutic agent in hypertension-associated diseases.

Stroke-prone renovascular hypertensive rat as an animal model for stroke studies: from artery to brain.

High blood pressure is a main risk factor for both initial and recurrent stroke. Compared to the post stroke situation in normotension, the brain lesion is larger in hypertension, and the treatments may not be as effective. Thus, the results from healthy individuals may not be directly applied to the hypertensive. In fact, the high prevalence of hypertension in stroke patients and its devastating effect urge the necessity to integrate arterial hypertension in the study of stroke in order to better mimic the clinical situations. The first step to do so is to have an appropriate hypertensive animal model for stroke studies. Stroke-prone renovascular hypertensive rat (RHRSP) introduced in 1998, is an animal model with acquired hypertension independent of genetic deficiency. The blood pressure begins to increase during the first week after constriction of bilateral renal arteries, and becomes sustained since around the 3rd month. Because the morphological and physiological changes of cerebral arteries are similar to those in hypertensive patients, the rats represent a higher than 60% incidence of spontaneous stroke. The animal model has several advantages: one hundred percent development of hypertension without gene modification, high similarity to human hypertension in cerebrovascular pathology and physiology, and easy establishment with low cost. Thus, the model has been extensively used in the investigation of ischemic stroke, and has been shown as a reliable animal model. This paper reviewed the features of RHRSP and its applications in the treatment and prevention of stroke, as well as the investigations of secondary lesions postischemic stroke.

Physical exercise improves functional recovery through mitigation of autophagy, attenuation of apoptosis and enhancement of neurogenesis after MCAO in rats.

BACKGROUND: Physical exercise improves functional recovery after stroke through a complex mechanism that is not fully understood. Transient focal cerebral ischemia induces autophagy, apoptosis and neurogenesis in the peri-infarct region. This study is aimed to examine the effects of physical exercise on autophagy, apoptosis and neurogenesis in the peri-infarct region in a rat model of transient middle cerebral artery occlusion (MCAO). RESULTS: We found that autophagosomes, as labeled by microtubule-associated protein 1A light chain 3-II (LC3-II), were evident in the peri-infarct region at 3 days after 90-minute MCAO. Moreover, 44.6% of LC3-positive cells were also stained with TUNEL. The number of LC3 positive cells was significantly lower in physical exercise group than in control group at 14 and 21 days after MCAO. Suppression of autophagosomes by physical exercise was positively associated with improvement of neurological function. In addition, physical exercise significantly decreased the number of TUNEL-positive cells and increased the numbers of Ki67-positive, a proliferative marker, and insulin-like growth factor-1 (IGF-1) positive cells at 7, 14, and 21 days after MCAO. CONCLUSIONS: The present results demonstrate that physical exercise enhances neurological function possibly by reduction of autophagosome accumulation, attenuation of apoptosis and enhancement of neurogenesis in the peri-infarct region after transient MCAO in rats.

Factors associated with severity on admission and in-hospital mortality after primary intracerebral hemorrhage in China.

BACKGROUND AND PURPOSE: Of the stroke types, intracerebral hemorrhage is the most debilitating and fatal. The aim of the current study was to determine factors that influence the severity and in-hospital mortality after primary intracerebral hemorrhage. METHODS: Data were collected retrospectively on 1268 patients with primary intracerebral hemorrhage admitted to stroke units at participating hospitals in Guangzhou between January 2005 and August 2008. Logistic regression analysis was used to determine factors associated with severity on admission and in-hospital mortality. RESULTS: Of the 1268 patients, 20·4% were reported to have a severe stroke on admission, and the in-hospital mortality rate was 12·5%. Severity on admission was strongly associated with Glasgow Coma Scale score on admission (odds ratio = 0·89, 95% confidence interval 0·85-0·94) and hematoma location. Notably, basal ganglia hemorrhages were associated with increased severity (odds ratio = 1·40, 95% confidence interval 1·03-1·90), and cerebellar hemorrhages were associated with reduced severity (odds ratio = 0·29, 95% confidence interval 0·10-0·84). In-hospital mortality was not only correlated with Glasgow Coma Scale score on admission (odds ratio = 0·79, 95% confidence interval 0·74-0·84) and basal ganglia location (odds ratio = 0·47, 95% confidence interval 0·26-0·83), but also with dysnatremia (odds ratio = 1·91, 95% confidence interval 1·08-3·40) and comorbidities such as upper gastrointestinal hemorrhage (odds ratio = 2·28, 95% confidence interval 1·33-3·91), pneumonia (odds ratio = 3·50, 95% confidence interval 2·17-5·63), urinary incontinence (odds ratio = 2·22, 95% confidence interval 1·40-3·51), and renal dysfunction (odds ratio = 2·28, 95% confidence interval 1·42-3·65). CONCLUSION: Glasgow Coma Scale score and hematoma locations were independently associated with severity on admission and in-hospital mortality after primary intracerebral hemorrhage. The study also highlights the deleterious effect of comorbidities on in-hospital mortality following primary intracerebral hemorrhage in China.

[Response to thymectomy and analysis of influencing factors in the treatment of children with myasthenia gravis].

OBJECTIVE: To evaluate the efficacy of thymectomy and relevant influencing factors in the treatment of children with myasthenia gravis through a long-term follow-up. METHODS: The clinical records of 59 patients undergoing expanded thymectomy for the treatment of myasthenia gravis (MG) between January 2003 and August 2009 were reviewed retrospectively. Their postoperative outcomes were categorized into complete stable remission (CSR), pharmacological remission (PR), improvement, no change and deterioration (including mortality). RESULTS: During a median follow-up period of 35 months, none of them died or deteriorated clinically among 53 patients with a postoperative follow-up. The overall remission rate was 69.8% and the effective rate 90.6%. No symptomatic relapse occurred among 16 patients in CSR. None of the ocular patients progressed to generalized MG while 16 thymectomized generalized MG developed from ocular MG. Both univariate and logistic regression analyses revealed that the preoperative duration of illness influenced the surgical curative effect (P < 0.05). Survival analysis indicated that the rates of overall remission were 56% or 88% at 24 months and 42% or 75% at 48 months among ocular MG and generalized MG respectively. According to Log-rank analysis, no difference in remission existed between two types of MG. CONCLUSION: Thymectomy is an effective and safe treatment in selected MG children, especially in those with a shorter illness duration.

Marine cyclotripeptide X-13 promotes angiogenesis in zebrafish and human endothelial cells via PI3K/Akt/eNOS signaling pathways.

Cyclotripeptide X-13 is a core of novel marine compound xyloallenoide A isolated from mangrove fungus Xylaria sp. (no. 2508). We found that X-13 dose-dependently induced angiogenesis in zebrafish embryos and in human endothelial cells, which was accompanied by increased phosphorylation of eNOS and Akt and NO release. Inhibition of PI3K/Akt/eNOS by LY294002 or L-NAME suppressed X-13-induced angiogenesis. The present work demonstrates that X-13 promotes angiogenesis via PI3K/Akt/eNOS pathways.

Peroxisome proliferator activated receptor (PPAR)-γ co-activator 1-α and hypoxia induced factor-1α mediate neuro- and vascular protection by hypoxic preconditioning in vitro.

Preconditioning-induced cellular adaptation is a new therapeutic strategy for ischemic stroke. This research aims to examine the role of peroxisome proliferator activated receptor (PPAR)-γ co-activator 1-α (PGC-1α) and hypoxia induced factor-1α (HIF-1α) in hypoxic preconditioning-induced protection. In this study, rat artery endothelial cells and neuronal PC12 cells were preconditioned with hypoxia before oxygen-glucose deprivation (OGD) insult. Cell viability, protein expression and oxidative stress were then evaluated. PGC-1α and HIF-1α were knocked down by RNA interference. We found that hypoxic preconditioning significantly reduced cell damage, enhanced the expression of PGC-1α, HIF-1α and VEGF and attenuated oxidative stress in endothelial and PC12 cells in OGD model. The protective effects of hypoxic preconditioning were hardly detected in HIF-1α or PGC-1α deficit cells. The loss of protection was accompanied with a significant loss of VEGF expression in HIF-1α or PGC-1α deficit PC12 cells and PGC-1α deficit endothelial cells as well as a considerable decrease of anti-oxidative effects in PGC-1α knocked-down endothelial cells. The present study demonstrated that both PGC-1α and HIF-1α played crucial roles in hypoxic preconditioning in endothelial and neuronal cells.