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 establish a reversed-phase high performance liquid chromatograph ( RP-HPLC ) method for determination of equilibrium solubility and oil/water partition coeficient of phloridzin in different solvents. Methods A RP-HPLC method was established to detect the concentration of phloridzin in water and different organic solvents. The partition coefficients in the n-octanol-water/buffer solution systems of phloridzin were determined by shaking flask method. The Inertsil ODS-3 (4.6 mm×150 mm, 5μm) column was used and the detection wavelength was 284 nm.The flow rate was 1.0 mL??min-1, and acetonitrile-0.05% phosphoric acid(30??70)was used as mobile phase. Results The equilibrium solubility of phloridzin was 2.07 mg??mL-1 in water and 838.63 mg??mL-1 in methanol at 25 ℃.A good linear relationship of phloridzin was obtained within the range of 0.054 9-1.098 0 μg.The regression equation was Y=2 152.9X+7.26 (r=0.999 9).The solubility values of phloridzin were higher in ethanol and propylene glycol than in other solvents. Conclusion RP-HPLC method is simple, quick and accurate for the determination of phloridzin.Phloridzin was almost insoluble in petroleum ether and poorly soluble in water.The equilibrium solubility is higher in methanol than in other solvents. The apparent distribution coefficient of phloridzin varies significantly with pH under the alkaline conditions but less in the acidic solution.

Objective To investigate the molecular mechanism of the glucocorticoid?induced osteoblasts apoptosis,and to develop the effective intervention measures. Methods The MC3T3?E1 cells were treated with different concentrations of dexamethasone for 24 hours,then the apoptosis rate was detected with TUNEL analysis,the intracellular expression of Bim and Bax were determined by Westen blot. In addition,MC3T3?E1 cells were randomly divided into Bim?siRNA group,negative control siRNA group and control group. Twenty?four hours after transfection,10-4mmol/L dexamethasone was added to each group of cells for another 24 hours administration. The apoptosis rate was analyzed using the TUNEL,the mito?chondrial transmembrane electric potential was detected by flow cytometry after JC?1 staining,the expression of Bax,Bcl?2 in mitochondrial and Cyt?C,AIF in cytosolic were determined by Western blot. Results The rate of osteoblast apoptosis and Bim expression in cells were both significantly in?creased with the dosage of dexamethasone,there was no significant difference between the groups in the expression of Bax;the rate of osteoblast apop?tosis after the expression of silence Bim was significantly lower than the negative control siRNA group and control group,the expression of Bax and Cyt?C,AIF in cytosolic were significantly reduced,and the mitochondrial transmembrane electric potential was increased. Conclusion Bim is the key molecules in hormone?induced apoptosis of osteoblasts ,the expression of silence Bim can inhibit dexamethasone induced osteoblasts apoptosis through the mitochondrial pathway.

Objective To observe the clinical efficacy of percutaneous vertebroplasty (PVP) with percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fracture(OVCF) by systematic review. Methods From September 2005 to March 2009,46 cases of fresh OVCF were treated. Patients were divided into 2 groups (A, B), according to Jikei grade, Genant semiquantitative method, injury vertebra number. Twenty-five cases(group A)were treated by PVP,8 males and 17 females with the age of 52 - 78 years (average 69). Vertebra segment of fracture was within T6 - L5 (14 in case thoracical vertebrae and 11 lumbar vertebrae). Twenty-one cases(group B)were treated by PKP,There were 6 males and 15 females with the age of 54 - 82 years (average 71). Vertebra segment of fracture was within T6 - L4 (12 in case thoracical vertebrae and 9 lumbar vertebrae). The clinical efficacy, incidence rate of complication, the anterior height of vertebrae body,visual analogue pain scale(VAS) ,ease of pain were measured preoperatively and at 6 weeks, 3 and 6 months and 1 year postoperatively between the two groups. Results All the patients were followed up for 12 -45 months with an average of 23.5 months. The average recovery of anterior height of vertebrae body was respectively(85.95 ± 4.31) % in group A and (93.64 ± 3.35) % in group B,which statistically difference in vertebral height between two groups (P ＜ 0.05). No statistical significant difference was seen in VAS, analgesic durg (AID) and ease of pain complication between two groups (P ＞0. 05). Statistical significant difference was noted in pre-postoperatively between intra-two groups (P ＜0. 05). Conclusions PVP and PKP can quickly relieve pain and enhance vertebral stability in treating thoracolumbar OVCF according to evaluation parameter, and have the similar therapeutic efficacy in treatment of OVCF with minimal invasion. However, PKP is superior in the recovery of vertebral height.