Diffuse lower-grade glioma is a diversified group of infiltrative brain tumors comprising WHO grades II and III astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. These tumors exhibit a wide range of clinical heterogeneity;thus, histopathological classification does not adequately predict clinical outcomes. In recent years, a number of molecular markers closely related to the clini-cal features and prognosis of gliomas have been discovered. These molecular markers include isocitrate dehydrogenase (IDH) muta-tion, chromosome 1p/19q codeletion, ATRX mutation, TERT promoter mutation, and MGMT promoter methylation. Furthermore, nu-merous studies focusing on the integrated molecular classification of diffuse lower-grade gliomas combined with these molecular markers have been conducted. Results indicate that integrated molecular pathological classification can improve the diagnostic and prognostic accuracy and facilitate therapeutic formulation. This paper reviews the research progress on integrated molecular classifica-tion of diffuse lower-grade gliomas.

Cancer stem cells are thought to be the seed of tumor formation, through complex signalings and cytokines in the surrounding microenvironment regulate the development and metastasis of tumor.Tumor stem cells have the characteristics of self-renewal and differentiation, the intracellular signaling pathways regulating self-renewal and differentiation of cancer stem cell include Wnt, Hedgehog signaling pathway.The tumor microenvironment is the dimensional environment surrounding the tumor,including the extracellular matrix, surrounding blood capillary,stromal cells ( fibroblasts, mesenchymal stem cells, tumor-associated endothelial cells, inflammatory cells) and cytokines secreted by stromal cells.Cancer stem cells maintain a close communication with the cells in the tumor microenvironment.In this paper, the cell surface maker of cancer stem cell,cancer stem cells and regulation of cytokine in the microenvironment,intracellular signaling pathways of cancer stem cells are reviewed to show complex regulatory networks in the tumor microenvironment.This review should help providing a new direction on specific cancer therapy for cancer stem cells in cacer treatment.

AIM To study whether cyproheptadine(Cyp) affects endocrine functions in reproductive system with gender difference. METHODS Sixty SD rats were randomly distributed into 3 groups according to gender, respectively, and they were administered NS(5 mL*kg-1*d-1), Cyp 2.4, 4.8 mg*kg-1*d-1 accordingly by ig for 14 d or 21 d. The serum levels of luteinizing hormone(LH), follicle stimulating hormone(FSH), testosterone(T), progesterone(P), estrodiol(E2) were measured by radio-immunoassay and the ultrastructure of gonadotropin-releasing hormone(GnRH) cells, gonadotropin cells, Leydig cells, Sertoli cells, luteal cells, granulocytes and so on were observed by electronmicroscopy and microscopy. The calmodulin(CaM) mRNA expression in hypothalamus-pituitary-testis axis(HPTA) was detected by reverse transcriptase-polymerase chain reaction. RESULTS Cyp(2.4 mg*kg-1*d-1×14 d, ig) increased serum LH concentration while decreased serum FSH, P concentrations in female rats. Cyp(4.8 mg*kg-1*d-1×14 d, ig)increased serum LH, T concentrations in males, and increased serum LH concentration while decreased serum FSH, E2 and P concentrations significantly in females. The retrograde changes of ultrastructure were observed in part of gonadotropin and ovary endocrine cells, while a stimulating one in testis endocrine cells. CaM mRNA expression levels were elevated in testis but not in hypothalamus and pituitary in male rats. CONCLUSIONCyp had a negative effect on endocrine function in females, but a positive one in males. The ultrastructure showed relevant changes in target gland. Cyp promoted CaM mRNA expression in testis,which had close connections with Cyp′s stimulative effect in HPTA.

Objective: To explore the relationship between prevalence of atrial fibrillation (AF), iskhemia stoke and CHA2DS2-VASc score in patients≥65 years in order to provide prevention and treatment basis in clinical practice. Methods: A total of 5016 patients admitted in our hospital from 2013-10 to 2015-10 were enrolled. The patients were divided into 2 groups: AF group, n=437 and Non-AF patients, n=4579; according to age, the patients were further assigned into 4 subgroups as <65 years subgroup, (65-74) years subgroup, (75-84) years subgroup and ≥85 years subgroup. The risk factors for AF occurrence were retrospectively studied. Results: Compared with the Non-AF group, the patients in AF group had the elder age and more male gender, both P<0.001; more patients combining with hypertension, coronary artery disease (CAD), diabetes, sick sinus syndrome and rheumatic heart disease, all P<0.001. Age, male gender, CAD, sick sinus syndrome and rheumatic heart disease were the independent risk factors for AF occurrence. Compared with Non-AF group, AF group showed the higher prevalence rate of ischemic stroke and the elder onset age, both P<0.01. For non-valvular AF, the ratio of patients with CHA2DS2-VASc score≥2 was higher than those with CHA2DS2-VASc score<2 and the rate of anticoagulant therapy was decreasing by age increasing, all P<0.001. Conclusion: Age, male gender, CAD, sick sinus syndrome and rheumatic heart disease were independently related to AF occurrence. Non-valvular AF patients had the higher risk for ischemic stroke than non-AF patients, anticoagulation therapy should be conducted at the early stage.

Objective The aim of our study was to investigate the effects and mechanisms of ghrelin on neovascularization in atherosclerosis plaque. Methods 30 male New Zealand rabbits were randomly divided into normal control group ( CON group) , atherosclerosis model group ( AS group) , and ghrelin treatment group ( ghrelin group) , and each group of 10 rabbits. The AS group and ghrelin group underwent balloon-induced arterial wall injury and then fed with high fat diet, the CON group was fed only on a regular diet. They were all fed for 3 months. Then the ghrelin group was given ghrelin 25μg·kg-1 ·d-1 , the other two groups received the same amount of sterile normal saline only. Four weeks later, body weight and blood lipids were detected. The thickness ratio of the intima to media was measured by HE staining. Degree of intra-plaque angiogenesis was evaluated by CD31+ cells immunohisto-chemistry. The vascular endothelial growth factor ( VEGF ) and vascular endothelial growth factor receptor 2 ( VEGFR2) were detected by quantitative realtime PCR and Western blot. The expressions of matrix metalloproteinase ( MMP)-2 and MMP-9 were detected by immunohistochemistry and Western blot. Results ( 1 ) No significant differences in body weight and blood lipids were found between the AS group and the ghrelin group(P>0. 05), but both items were significantly higher than those of the CON group(P<0. 05). (2)The thickness ratio of the intima to media in the ghrelin treated group was distinctly less than that in the AS group(P<0. 05). (3)Compared with the AS group, the ghrelin group showed significantly decreased microvascular density and the expressions of VEGF and VEGFR2 (P<0. 05). (4)Compared with the AS group, ghrelin dramatically inhibited the plaque contents of MMP-2 and MMP-9 ( P<0. 05 ). Conclusions Ghrelin is able to inhibit the growth of neovascularizationin in the atherosclerotic plaque and the development of plaque. And these beneficial effects derive from downregulation of VEGF, VEGFR2, MMP-2, and MMP-9 at the advanced stage of atherosclerosis in rabbits.

Voltage-gated sodium channels (VGSCs), which are widely distributed in the excitable cells, are the primary mediators of electrical signal amplification and propagation. They play important roles in the excitative conduction of the neurons and cardiac muscle cells. The abnormalities of the structures and functions of VGSCs can change the excitability of the cells, resulting in a variety of diseases such as neuropathic pain, epilepsy and arrhythmia. At present, some voltage-gated sodium channel blockers are used for treating those diseases. In the recent years, several neurotoxins have been purified from the venom of the animals, which could inhibit the current of the voltage-gated sodium channels. Usually, these neurotoxins are compounds or small peptides that have been further designed and modified for targeted drugs of sodium channelopathies in the clinical treatment. In addition, a novel cysteine-rich secretory protein (CRBGP) has been isolated and purified from the buccal gland of the lampreys (Lampetra japonica), and it could inhibit the Na+ current of the hippocampus and dorsal root neurons for the first time. In the present study, the progress of the sodium channelopathies and the biological functions of voltage-gated sodium channel blockers are analyzed and summarized.
Animals ; Channelopathies ; physiopathology ; Hippocampus ; drug effects ; Neurons ; drug effects ; Neurotoxins ; pharmacology ; Venoms ; chemistry ; Voltage-Gated Sodium Channel Blockers ; pharmacology

Objective: To determine the transdermal absorption of phloretin and ligustilide in Fufang phloretin cream.Methods: In vitro percutaneous absorption test using the Franz intelligent transdermal absorption apparatus was adopted, an HPLC method was used to determine the contents of phloretin and ligustilide in the accepting solution at different time points, and then the cumulative release amount and the total penetration amount were calculated to evaluate the percutaneous absorption behavior.Results: Phloretin and ligustilide showed a good linearity within the range of 0.044 2-4.42 μg·ml-1(r=0.999 9) and 0.048 7-4.87 μg·ml-1(r=0.999 9), respectively, the average recovery was 99.85% and 99.92%, and RSD was 0.67% and 0.66% (n=9), respectively.The in vitro permeation behavior of phloretin and ligustilide through the skin of rats fit Higuchi equations(r>0.9), suggesting a good linear correlation between the cumulatine penetration amount (Qn) and (time).Conclusion: Fufang phloretin cream has a good percutaneous permeation property in vitro.

Objective: To explore the relationship between serum level of high-sensitivity cardiac troponin T (hs-cTnT) and atrial ifbrillation (AF) occurrence in patients with stable coronary artery disease (CAD).
Methods: A total of 1011 patients with stable CAD treated in our hospital from 2013-01 to 2015-09 were retrospectively studied. According to quartiles of hs-cTnT, the patients were divided into 4 groups: Group① the patients with hs-cTnT≤7ng/L, n=283, Group② hs-cTnT 7-10ng/L,n=238, Group③ hs-cTnT 10-15ng/L,n=272 and Group④ hs-cTnT>15ng/L,n=218. The relationship between hs-cTnT level and AF occurrence rate was studied; the risk factors for AF occurrence were explored by multi stepwise Logistic regression analysis.
Results: There were 127/1011 (12.6%) patients combining AF and 884 (87.4%) with simple type stable CAD. AF patients had the higher serum level of hs-cTnT than non-AF patients 17.0 (12.0, 25.0) ng/L vs 10.0 (7.0, 13.0) ng/L,P<0.01. With baseline hs-cTnT level increasing, AF occurrence rates were elevated from group① to Group④ as 4.6% (13/283), 4.6% (11/238), 11.0% (30/272) and 33.5% (73/218), Ptrend<0.05. Multi stepwise Logistic regression analysis revealed that with adjusted common risk factors of age and gender, the risk for stable CAD patients suffering from AF in Group④ was 5.324 times higher than group① (95% CI 2.285-12.405,P<0.01).
Conclusion: Increased serum level of hs-cTnT was closely related to AF occurrence in patients with stable CAD.

Objective: To explore the relationship between lower extremity atherosclerosis disease (LEAD) and cardiovascular risk factors in elder people.
Methods: A total of 700 consecutive patients receive lower extremity Color Doppler ultrasound in our hospital from 2013-05 to 2014-11 were investigated. The patients were divided into 3 age groups: Young and middle group, n=83, Elder group, n=377 and Senile group, n=240. Based on ultrasound scoring system, the patients were divided into 4 groups: Normal group, n=112, Mild atherosclerosis (Mild) group, n=81, Moderate group, n=466 and Severe group, n=41. The cardiovascular risk factors among different groups were compared.
Results: Multivariate unconditional logistic regression analysis showed that age, smoking, history of diabetes, uric acid (UA), ankle-brachial index (ABI) were the independent risk factors for LEAD (B=0.144, 1.496, 0.963, 0.004, -2.510; 95% CI: 1.120-1.190, 2.257-8.824, 1.456-4.716, 1.001-1.007, 0.012-0.534;P=0.000, 0.000, 0.001, 0.006, 0.009 respectively. Ordinal logistic regression analysis indicated that age, male gender, smoking, ABI, UA, history of hypertension were related to the severity of atherosclerosis (B=0.130, 0.737, 0.592, -3.365, 0.003, 0.735; 95% CI: 0.097-0.162, 0.222-1.252, 0.052-1.132, -4.674 to -2.055, 0.001-0.005, 0.313-1.157;P=0.000, 0.005, 0.032, 0.000, 0.005, 0.001 respectively. Compared with Young and Middle groups, Elder and Senile groups had increased rates of moderate and severe arteriosclerotic lesions; compared with Elder group, Senile group presented the higher incidence of moderate and severe lesions, allP<0.01. With elevated age, the severity score of LEAD increased accordingly,P<0.01.
Conclusion: Lower extremity atherosclerosis lesions were more severe in elder patient, and it was particularly severe in senile patients.