Inhibition of EphA4 reduces vasogenic edema after experimental stroke in mice by protecting the blood-brain barrier integrity.

Cerebral vasogenic edema, a severe complication of ischemic stroke, aggravates neurological deficits. However, therapeutics to reduce cerebral edema still represent a significant unmet medical need. Brain microvascular endothelial cells (BMECs), vital for maintaining the blood-brain barrier (BBB), represent the first defense barrier for vasogenic edema. Here, we analyzed the proteomic profiles of the cultured mouse BMECs during oxygen-glucose deprivation and reperfusion (OGD/R). Besides the extensively altered cytoskeletal proteins, ephrin type-A receptor 4 (EphA4) expressions and its activated phosphorylated form p-EphA4 were significantly increased. Blocking EphA4 using EphA4-Fc, a specific and well-tolerated inhibitor shown in our ongoing human phase I trial, effectively reduced OGD/R-induced BMECs contraction and tight junction damage. EphA4-Fc did not protect OGD/R-induced neuronal and astrocytic death. However, administration of EphA4-Fc, before or after the onset of transient middle cerebral artery occlusion (tMCAO), reduced brain edema by about 50%, leading to improved neurological function recovery. The BBB permeability test also confirmed that cerebral BBB integrity was well maintained in tMCAO brains treated with EphA4-Fc. Therefore, EphA4 was critical in signaling BMECs-mediated BBB breakdown and vasogenic edema during cerebral ischemia. EphA4-Fc is promising for the treatment of clinical post-stroke edema.

Analysis of cancer incidence in Zhejiang cancer registry in China during 2000 to 2009.

OBJECTIVE: The Zhejiang Provincial Cancer Prevention and Control Office collected cancer registration data during 2000 to 2009 from 6 cancer registries in Zhejiang province of China in order to analyze the cancer incidence. METHODS: Descriptive analysis included cancer incidence stratified by sex, age and cancer site group. The proportions and cumulative rates of 10 common cancers in different groups were also calculated. Chinese population census in 1982 and Segi's population were used for calculating age-standardized incidence rates. The log-linear model was used for fitting to calculate the incidence trends. RESULTS: The 6 cancer registries in Zhejiang province in China covered a total of 60,087,888 person-years during 2000 to 2009 (males 30,445,904, females 29,641,984). The total number of new cancer cases were 163,104 (males 92,982, females 70,122). The morphology verified cases accounted for 69.7%, and the new cases verified only by information from death certification accounted for 1.23%. The crude incidence rate in Zhejiang cancer registration areas was 271.5/105 during 2000 to 2009 (male 305.41/105, female 236.58/105), age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 147.1/105 and 188.2/105, the cumulative incidence rate (aged from 0 to 74) being 21.7%. The crude incidence rate was 209.6/105 in 2000, and it increased to 320.20/105 in 2009 (52.8%), with an annual percent change (APC) of 4.51% (95% confidence interval, 3.25%-5.79%). Age-specific incidence rate of 80-84 age group was achieved at the highest point of the incidence curve. Overall with different age groups, the cancer incidences differed, the incidence of liver cancer being highest in 15-44 age group in males; the incidence of breast cancer was the highest in 15-64 age group in females; the incidences of lung cancer were the highest in both males and females over the age of 65 years. CONCLUSIONS: Lung cancer, digestive system malignancies and breast cancer are the most common cancers in Zhejiang province in China requiring an especial focus. The incidences of thyroid cancer, prostate cancer, cervical cancer and lymphoma have increased rapidly. Prevention and control measures should be implemented for these cancers.

[A safety assessment on adverse reaction of recombinant B-subunit/inactivated whole cell oral cholera vaccine among non-infected population].

OBJECTIVE: To observe the safety of recombinant B-subunit/inactivated whole cell (rBS/WC) oral cholera vaccine among non-infected population. METHOD: A method of double-blind and case control was conducted randomly. 3041 non-infected persons who aged from 5- to 60-years-old were divided randomly into 3 groups, including 2 vaccine groups and 1 placebo group. The vaccine and placebo were taken respectively by vaccine groups and placebo group on the 1st, 7th and 28th day in every months of sequential 3 months. The adverse reaction was observed in sequential 3 days after intaking orally. The follow-up interviews were conducted in 1, 2, 3 months. RESULTS: No severe adverse reaction was occurred. The rate of adverse reaction was 1.70% in vaccine groups, 1.74% in placebo group. There was no statistically significant difference between two groups (chi2=0.013, P=0.909). The adverse reaction were mainly abdominal pain, diarrhea, partly anaphylaxis, and the others of dizziness, fatigue, weakness. Most people recovered within short time without any medical treatment. The adverse reactions might be related to psychogenic reaction. CONCLUSION: The safety of oral rBS/WC cholera vaccine among non-infected population was pretty good.