Brain natriuretic peptide (BNP) is one of the most sensitive and specific laboratory indicators during cardiac dysfunction.N-Terminal pro-brain natriuretic peptide (NT-proBNP) is the N-terminal precursor of BNP.The functions of both are not consistent,but its physicochemical properties are superior to BNP.Now it has been widely used in the diagnosis and treatment monitoring of cardiovascular diseases.In the field of stroke,the testing and application of BNP,especially NT-proBNP is less.This article reviews the roles of NT-proBNP in cardio-cerebrovascular diseases,especially in ischemic cerebrovascular disease.

Objective To explore the effects of granulocyte colony stimulating factor (G-CSF)on chronic cerebral ischemia in rats,and its possible mechanism.Methods Chronic cerebral ischemia (2-VO) model was prepared and bilateral external jugular veins were isolated.A total of 30 rats were divided into 2 groups at random sham group (received no intervention,n=15) and operative group (received G-CSF or PBS through external jugular vein injection,n=15).At 6 weeks after operation,the rats in operative group were divided into G--CSF group (received G-CSF 10 mg/L,1 ml · kg-1 · d-1,1 times every 24 h for,3 times) and PBS control group (received PBS 10 mg/L,1 ml ·kg 1 · d-11,1 times every 24 h for 3 times).At 8 weeks after the operation,morris water maze was carried out to evaluate the learning and memory ability of the rats.The cell proliferation,threedimensional vascular distribution,ischemic neuronal apoptosis,cell morphological changes in ischemic area and the plasma VEGF levels were detected to explore the possible mechanisms.Results In morris water maze,escape latency at the 2rd to 5th day were significantly lower in G-CSF group than the PBS group (all P＜0.05).The swimming time spent in the first quadrant in G-CSF group was significantly longer than the PBS group (P＜0.05).There was a significant difference in the number of BrdU positive cells in the ischemical area between the G-CSF group and the control group [(27.7±4.76) vs.(10.4 ± 3.7),P =0.030).Three-dimensional quantitative measurements of vascular structure showed that the capillary diameters was smaller in the G-CSF group than in the PBS group [(2.90±0.20) μm vs.(3.45±0.26) μm,P=0.020] and the number of branch points in the boundary regions of ischemia had a significant difference in the G-CSF group compared with the control group [(207.82±10.73) /0.002 mm3 vs.(162.10±9.31) /0.002mm3,P=0.005].Threedimensional cerebral vessel surface area in the ipsilateral hemisphere was increased in the G-CSF group compared with the PBS group [(86498±2896) μm2/0.002 mm3vs.(73976±3826) μm2/0.002 mm3,P=0.003].The number of apoptotic cells in G-CSF group was decreased compared with the PBS group [(32.10±6.70) vs.(56.30±11.20),F=11.89,P=0.043].The electron microscope morphological observations showed inflammatory edema in intercellular gap was significantly reduced in the G-CSF group compared with the PBS group.The level of plasma VEGF was significantly increased in the G-CSF group compared with the PBS group [(58.81±6.61) ng/L vs.(20.81±4.35)ng/L,P=0.025].Conclusions G--CSF can improve the learning and memory ability in the chronic cerebral ischemic rats,and its possible mechanism might involve the nerve protection and the vascular regeneration associated with the VEGF.There is a great prospect for G-CSF in the therapy of chronic cerebral ischemic disease.

To investigate molecular epidemiology of DuCV in Cherry Valley ducks in China,the complete genomes of six DuCV strains,which were detected from Cherry Valley ducks in China between 2007 and 2008,were sequenced.Sequence and phylogenetic analysis were carried out to compare these six strains with another 27DuCV strains from Mulard duck,Muscovy duck,Pekin ducks and Mule duck.The analysis showed that the six DuCV strains exhibited typical genetic features of the family of DuCV,such as a stem-loop structure,three major open reading frames (Rep,Cap and ORF3),four intergenic repeats and the conserved motifs for rolling circle replication and for the dNTP binding domain located in the Rep protein.Phylogenetic analysis of the nucleotide sequences of the complete genome and Cap gene of these strains together with those that have been previously published demonstrated two distinct DuCV genotypes.The DuCV strains with complete genomes containing 1988and 1989 nucleotides clustered in genotype A,whereas the strains with complete genomes containing 1991,1992,1995 and 1996 nucleotides lay in genotype B.The six DuCV strains from Cherry Valley ducks were divided into the two groups.The results of the study provides some insight into the variation of DuCVs in Cherry Valley ducks.

Objective To analyze the mutations of IDS gene in a mucopolysaccharidosis type Ⅱ (MPS Ⅱ) family and to make prenatal diagnosis on the high-risk fetus which has been pregnant for eleven weeks.Methods IDS gene was analyzed by bidirectional DNA sequencing in 2 patients and their mother,and 5 unaffected individuals.Prenatal diagnosis for the high-risk fetus was performed by chorionic villus sampling after the genotypes was identified.Results The mutation c.344delA (N115fsX15) was detected in the two patients,and the mother of patients carried the heterozygous c.344delA (N115fsX15) mutation.None of the mutant was detected in the 5 unaffected subjects.The fetus carried c.344delA (N115fsX15) heterozygous mutation and was a carrier.Conclusion The deletion mutation c.344delA (N115fsX15) is causative to the pedigree of MPS Ⅱ,and prenatal diagnosis is the efficient method to avoid defect birth.

Objective To investigate the effect of autologous bone marrow-derived endothelial progenitor cell (EPC) transplantation on neurological outcomes in cerebral ischernia in rats and its poss le mechanisms.Methods Autologous bone marrow-derived EPC was cultured in vitro and it was labeled with 5-bromodeoxyuridine (BrdU).A middle cerebral artery occlusion (MCAO) model was induced by the intraluminal suture method.The rats in a EPC group transplanted autologous EPC (106/ml/kg) via external jugular veins,those in a control group were injected with phosphate buffered saline (1 ml/kg),and those in a sham operation group (n =15)were not treated.The modified neurological severity score (mNSS) was used to observe the neurological changes of the rats.BrdU immunohistochemical staining was used to evaluate EPC proliferation and differentiation.Three-dimensional confocal image analysis was used to detect the vascular structure and density in cerebral ischemic areas.TUNEL staining was used to detect the apoptotio cells in ischernic brain tissue.Enzyme-linked immunosorbent assay was used to detect the concentration of plasma vascular endothelial growth factor VEGF).Results The mNSS in the EPC group was siginficantly lower than that in the control group (at day 8:6.43 ±0.69 vs.8.86 ±0.95,q =2.673,P=0.035; at day 14:4.55 ±0.89 vs.6.73 ± 1.06,q =5.360,P =0.035).The number of BrdU positive cells in the EPC group was significantly higher than that in the control group (42.2±5.76 vs.25.67±5.49,q=4.020,P=0.030).The capiilary diameter in the EPCgroup was significantly smaller than that in the control group (4.51 ± 0.21 μm vs.6.34 ± 0.24 μm,q =3.980,P =0.003); the density of blood vessels (212.64 ± 8.02/0.002 mm3 vs.153.60 ± 7.21/0.002 mm3; q =9.670,P =0.001 ) and the total surface area of microvessel (92 013 ± 5 132 μm2/0.002 mm3 vs. 71 366 ±4 538 μm2/0.002 mm3; q=4.180,P=0.014) were significantly higher or more than those in the control group.The number of apoptotic cells in the EPC group was significantly less than that in the control group (36.26 ± 6.91 vs.78.34 ± 7.21; t =-4.834,P =0.003).The plasma VEGF concentration in the EPC group was significantly higher than that in the control group (54.91 ± 5.71 pg/ml vs.13.81 ± 4.25 pg/ml,q =12.300,P=0.002).Conclusions Autologous EPC transplantation has a protective effect on ischemic brain tissue in rats.It may be associated with VEGF related angiogenesis and neuroprotection.It has an important application prospect in the treatment of ischemic cerebrovascular disease.

Objective To study the effect of endothelial progenitor cells on the behavior of chronic cerebral ischemic rats. Methods Adult rats were treated using the protocol of chronic cerebral ischemic model. Then translated the endothelial progenitor cells in vein to them, and Morris water maze was carried out to test the learning and merrory ability of the rats. The cell proliferation, vascular distribution and the plasma VEGF levels were day of 2nd to 5th of experimental group ( EPC group ) were significantly shorter than the control group ( PBS group), which were(44.45 ±9.44)s,(38.32±1.51)s,(34.95 ±6.76)s,(24.46 ±5.47)s and (52.79±6.47 ) s, ( 43.15 ± 11.21 ) s, ( 50.29 ± 11.41 ) s, ( 53.75 ± 7.35 ) s, (P ＜ 0.01 ) respectively. The time of EPC group spend in the first quadrant were significantly longer than that of the PBS group, which were (26. 76 ±of the EPC group( 26.8 ± 5.76 ) was higher than that of the conrespondering areas in the control group( 12.17 ±ments of capillaries were (P＜0.05) shorter in the PBS groups( (3.4 ±0.24) μm) than in the EPC groups( (2.8± 0.2 )μm) significantly, EPC group could significantly (P ＜ 0.05 ) increased the number of branch points in the boundary regions of ischemia compared with the number in the PBS group (respectively (210. 1 ± 13.80 ) and (164.2 ± 12.3 )). Three-dimensional cerebral vessel surface area in the ipsilateral hemisphere significantly increased in the EPC group compared with the PBS group (respectively (84365 ± 3897 )μm2/0. 002mm3 and group in the plasma VEGF levels ( ( 63.91 ± 6.71 ) pg/ml; ( 21. 81 ± 4.25 ) pg/ml, respectively (P ＜ 0.05, P ＜0.01 ). Conclusion There are positive behavioral effects of endotbelial progenitor cells in chronic cerebral ischemic rats. The possible mechanisns mavbe involve the nerve protection and regeneration of the vascular associated with the VEGF. The endothelial progenitor cells maybe have a great prospect in the therapy of chronic cerebral ischemic disease.

ObjectiveTo explore the curative effects of Puerarin Injection associated with Irbesartan on decompensated chronic cor pulmonale heart failure. MethodsA total of 168 cases conforming to the diagnostic standards were randomized into control group (92 cases) and therapy group (76 cases). In the control group: Based on the results of sputum and X-ray, broad-spectrum antibiotics were firstly selected and used for 3 days after admission. Then sensitive antibiotics were selected according to the results of sputum culture and drug sensitivity test. Medicine for relieving cough and asthma, and apophlegmatisant were used routinely. Patients with heart failure were treated with Digoxin or diuresis. In addition to the above treatments, the therapeutic group were treated with Puerarin Injection 600mg and Irbesartan 75mg once a day. The two groups were both treated for 20 days. Results①The incipient slope, 0.8 slope, 0.5 slope and the minimal surplus were all significantly changed (P＜0.01) in therapeutic group after the treatment. There were significant difference in the incipient slope, 0.8 slope, 0.5 slope and the minimal surplus before and after treatment both in the control group and therapeutic group. ②The plasma viscosity and blood viscosity decreased observably (P＜0.01) after the treatment in the therapeutic group, and more obviously than that in the control group (P＜0.01). ③The arterial oxygen pressure (PaO2) and arterial oxygen saturation (SaO2) in the therapeutic group were enhanced more prominently than that of the control group (P＜0.01). ④The mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) decreased obviously in the therapeutic group after the treatment, and more observably than those in the control group (P＜0.01). ⑤The cardiac output and cardiac index were improved prominently in the therapeutic group after the treatment, and more obviously than that of the control group (P＜0.01). ⑥The heart functional capacity (NYHA) improved significantly after the treatment both in the control group and the therapeutic group (P＜0.05). ConclusionsPuerarin Injection and Irbesartan could remarkablely change the erytlu'ocyte deformabifity, improve the hemorheology, lower pulmonary hypertension, and improve the cardiac function and the clinical efficacy in decompensation stage.

Objective To explore the clinical features of patients with vertebrobasilar dolichoectasia (VBD).Methods Patients diagnosed with posterior circulation ischemia in our hospital from October 2008 to January 2012 were consecutively collected and were divided into the VBD group and the non-VBD (NVBD) group.Clinical manifestations,risk factors,hemodynamic parameters and neuroimaging features were collected.Results (1) Statistical difference was observed in dyslipidemia,hypertension and the history of diabetes in the two groups (P ＜ 0.05).(2) The cerebral hemodynamic features of the VBD patients were as the following:decreased peak systolic velocity of vertebral artery and basilar artery and decreased systolic/diastolic ratio.Statistical difference was showed in the average peak flow velocity(Vm),pulsatility index(PI) and resistance index(RI) (P =0.036,0.032,0.032,respectively).(3) The main clinical manifestations of VBD were ischemic cerebrovascular disease,hemorrhagic cerebrovascular disease,oppression,brain damage symptoms and hydrocephalus.(4) The diagnosis in most of the VBD patients was confirmed by neural imaging and MRI was the first choice.Conclusion The VBD patients have relative unique clinical features.MRI should be the first choice for neuroimaging.

Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies worldwide with very poor prognosis. It is generally accepted that the progression of HCC is a long-term process with accumulation of multiple genetic and epigenetic alterations, which further lead to the activation of critical oncogenes or inactivation of tumor suppressor genes. HCC is characterized with multiple cancer hallmarks including their ability to proliferate, anti-apoptosis, invade, metastasis, as well as the emerging features such as stem cell properties and energy metabolic switch. The irreversible alterations at genetic level could be detected as early as in the pre-neoplastic stages and accumulate during cancer progression. Thus, they might account for the cancer initiating steps and further malignant transformation. In addition to genetic alterations, epigenetic alterations can affect the cancer transcriptome more extensively. Alterations in DNA methylation, histone modification, miRNAs, RNA editing, and lncRNAs might result in disrupted gene regulation networks and substantially contribute to HCC progression. In this review, the genetic and epigenetic alterations which significantly contribute to the malignant capabilities of HCC will be updated and summarized in detail. Further characterization of those critical molecular events might better elucidate the pathogenesis of HCC and provide novel therapeutic targets for treatment of this deadly disease.
Carcinoma, Hepatocellular ; genetics ; metabolism ; pathology ; Chromosome Aberrations ; Disease Progression ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; genetics ; Humans ; Liver Neoplasms ; genetics ; metabolism ; pathology ; Models, Genetic ; Mutation

Objective To screen the high specific and sensitive monitoring indications in the diagnosis of intestinal barrier dysfunction.Methods A total of 70 critical patients with intestinal barrier dysfunction and acute physiology and chronic health evaluation (APACHE) Ⅱ score≥8 and over the same period 41 patients without intestinal barrier dysfunction and APACHE Ⅱ score≤6 were recruited.The general information,histories,symptoms,physical signs,24 hours urine output and the condition of mechanical ventilation treatment were recorded.The venous blood was taken for bacteria culture,white blood cell counting,creatinine level,diamine oxidase (DAO) activity,D-lactic acid,intestinal fatty acid binding protein (IFABP) and endotoxin level testing.The urine was taken for urinary IFABP level testing.Twenty-four hours urine was reserved for 24 hours total urinary IFABP testing.The factors which might influence intestinal barrier dysfunction were analyzed by univariate analysis and multivariate analysis.The measurement data were analyzed by t test and the count data were analyzed by x2 test.The factors were screened according to receiver operating characteristic (ROC) curve.Results The factors related with intestinal barrier dysfunction were white blood cell counting (OR=3.971,P=0.046),plasma endotoxin level (OR=7.857,P=0.005)and 24 hours total urinary IFABP (OR=11.154,P=0.001).The areas under the ROC curve (AUC)of plasma endotoxin level and 24 hours total urinary IFABP were 0.852 and 0.820 respectively (both P＜0.01).The critical value was 8.0 pg/ml and 17.12 ng respectively.The sensitivity was 97.8％ and 84.4％.The specificity was 66.7％ and 72.7％.Conclusion Once critical patients presented certain gastrointestinal symptoms and physical signs with plasma endotoxin level ＞8.0 pg/ml and or 24 hours total urinary IFABP ＞17.12 ng,which might indicate intestinal barrier dysfunction.