Twenty-five compounds of novel quinoxaline-based scaffold with antiplatelet activity were designed and synthesized on the basis of previous quinoxaline analogues, and the structures were confirmed by ¹H NMR, ¹³C NMR, and MS. The antiplatelet activity was evaluated, structure-activity relationship (SAR) study was summarized and the selectivity of PAR4 was confirmed by calcium mobilization assays. It was indicated that compound 14a, 14g, 13i, 13p showed moderate activity against PAR4, especially, the activity of compound 14g (IC₅₀ = 0.26 μmol·L^-1) was 6.7 times than the lead compound A (IC₅₀ = 1.73 μmol·L^-1). Therefore, 2,3-dihydro-[1,4]dioxino[2,3-g]quinoxaline and [1,3]dioxolo[4,5-g]quinoxaline derivatives are promising compounds for the discovery of novel antiplatelet agents. It is worthy of further research to develop highly effective and selective PAR4 antagonists.

Objective To investigate the correlation between obstructive sleep apnea syndrome(OSAS)with myocardial ischemia and arrhythmia.Methods To observe the occuring rate of premature beats and change of ST- segment,90 eases of OSAS patients were detected by the polysomnogram(PSG)and dynamic electrocardiogram at the same time.Results Total morbidity of myocardial ischemia was 32.2 % in OSAS patients,and it was 59.4 %, 15.8 %,20 % in serious,moderate and mild groups respectively.There was a statistically significant difference be- tween the three groups and the control group(P0.05).Conclusion As one of the risky factors of cardiovascular diseases,OSAS can induce myocardial ischemia and arrhythmia.

To develop an analytic method for qualitative and quantitative analysis of dodecatetraenamides A, B in 42 samples of two official species of Asari Radix et Rhizoma( ARR) (37 samples of Asarum heterotropoides var. mandshuricum with different collection time and 5 samples of Asarum sieboldiivar. seoulense). The HPLC-IT-TOF-MS/MS methods for the qualitative and UPLC-PDA methods for the quantitative analysis were established. Dodecatetraenamides A, B were identified by comparing the retention time, UV absorption spectrum and quasi-molecular ion peak [ M + H]+ with the reference compound using HPLC-IT-TOF-MS/MS. The content of dodecatetraenamides A and B in ARR were determined by UPLC-PDA. The separation was successfully carried out on a ACQUITY UPLC BEH C18 (2.1 mm x 100 mm, 1.7 µm) column eluted with mobile phases of water (A) and acetonitrile (B) in gradient program (0-3 min, 35% B; 3-5 min, 35%-36% B; 5-6 min, 36%-43% B; 6 min-11 min 43% B; 11-12 min, 43%-100% B). The column temperature was 45 °C, and the detection wavelength was set at 254 nm. The flow rate was 0.6 mL · min(-1). On one level mass spectrometry scanning, the results showed that the quasi-molecular ion [M + H] + of both dodecatetraenamides A and B were m/z 248.20. The quantitative method with UPLC-PDA has made the baseline separation of the constituents, which were reported as mixtures in the most literatures. The average recovery of dodecatetraenamides A and B were 97.90% and 99.86%, the relative standard deviation were 0.4% and 1.1%, respectively. The contents of dodecatetraenamides A, B in all ARR samples was in the range of 0.11-3.89 and 0.24-6.65 mg · g(-1). Their contents reduced with the extension of storage time. Compared with the samples of 2013, the average content of the two constituents in the samples collected in year 2002-2003 reduced 34% and 36%, respectively (P < 0.05). Compared the A. sieboldii var. seoulense and A. heterotropoides var. mandshuricum with the same collective time and production area, the average contents of the two constituents in latter were up to (1.59 ± 0.75) mg · g(-1) and (2.90 ± 1.17) mg · g(-1), respectively, significantly higher than that in A. sieboldii var. seoulense (dodecatetraenamide A were (0.78 ± 0.52) mg · g(-1), dodecatetraenamide B were (1.69 ± 0.83) mg · g(-1)) (P < 0.05). The content of the dodecatetraenamide A in overground part was in the range of 0.11-0.33 mg · g(-1), dodecatetraenamide B was 0. 24-0.60 mg · g(-1), which were much lower than that of the underground part of ARR (dodecatetraenamide A was in the range of 0.73-3.89 mg · g(-1), dodecatetraenamide B was 2.11-6.24 mg · g(-1)). The method was certified to be simple, accurate and reliable and could be used for qualitative and quantitative analysis of dodecatetraenamide A and B in different species of ARR, also can be used for the comprehensive quality control of traditional Chinese medicine, Asari Radix et Rhizoma.
Amides ; chemistry ; Asarum ; chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Mass Spectrometry ; Molecular Structure ; Rhizome ; chemistry

OBJECTIVETo investigate the impact of intrauterine infection induced by LPS injection on long-term brain development of premature rats.

METHODSEighteen day-gestation pregnant rats were randomly assigned to a control group receiving an intraperitoneal injection of normal saline, and two infection groups that were intraperitoneally injected with 0.3 mg/kg or 0.6 mg/kg LPS. Twenty-four hours after injection, 7 pregnant rats of each group were sacrificed. The pathological changes of the placenta after hematoxylin and eosin staining were observed under a light microscope. The neural cell apoptosis of fetal brains was examined by the TUNEL assay. The remained pregnant rats were induced to labour before 21 gestation days. The long-term brain development of premature rats was tested with the Y type electric maze on postnatal day 42.

RESULTSObvious pathological changes were observed in the placenta in the infection groups. The apoptotic neural cells in the fetal brain increased in the infection groups compared with that in the control group (32.41+/-5.36 in the 0.3 mg/kg infection group and 66.41+/-7.61 in the 0.6 mg/kg infection group vs 8.00+/-0.36 in the control group; P<0.01). The number of trials to criterion in the Y type maze test in the infection groups was much more than that in the control group [117.8+/-8.7 (0.3 mg/kg infection group) and 194.4+/-13.7 (0.6 mg/kg infection group) vs 56.8+/-3.7 (control group); P<0.01]. The number of correct reactions in memory retaining in the infection groups was lower than that in the control group (0.62+/-0.09 in the 0.3 mg/kg infection group and 0.37+/-0.09 in the 0.6 mg/kg infection group vs 0.92+/-0.06 in the control group; P<0.05).

CONCLUSIONSIntrauterine infection can cause fetal rats' neural cell apoptosis and affect adversely long-term brain development of neonatal rats.

Animals ; Apoptosis ; Bacterial Infections ; physiopathology ; Blood-Brain Barrier ; Brain ; growth & development ; pathology ; Female ; Maze Learning ; Neurons ; pathology ; Pregnancy ; Pregnancy Complications, Infectious ; physiopathology ; Rats ; Rats, Wistar ; Uterus ; microbiology

BACKGROUNDMultiple epiphysis dysplasia (MED) is a common skeletal dysplasia with a significant locus heterogeneity. In the majority of clinically defined cases, mutations have been identified in the gene encoding cartilage algometric matrix protein (COMP).

METHODSFive patients were included in the study. Linkage analysis and mutation analysis of the COMP gene were conducted in the patients and their family members.

RESULTSWe have identified a novel mutation in axon 14 of COMP gene in the family.

CONCLUSIONSThis mutation produced a severe MED phenotype with marked short stature, early onset osteoarthritis, and remarkable radiographic changes. Our results extended the range of disease-causing mutations in COMP gene and contributed more information about relationship between mutations and phenotype.

Adolescent ; Asian Continental Ancestry Group ; Cartilage Oligomeric Matrix Protein ; genetics ; Female ; Humans ; Male ; Osteochondrodysplasias ; genetics ; Pedigree ; Point Mutation ; genetics

OBJECTIVETo examine the influence of vascular endothelial growth factors (VEGF) in controlling the growth of an experimental osteosarcoma in mice by performing retrovirus-mediated sFlt-1 gene modification.

METHODSFrom March to October 2010 human osteosarcoma G-292 cells were in vitro infected with retroviral vectors encoding soluble Flt-1 or LacZ gene before transplanted into proximal tibiae of immune deficient SCID mice to establish experimental orthotopic osteosarcoma. Daily observation and biweekly microCT were performed to monitor tumor development and progression till sacrifice at 8 weeks after tumor cell inoculation for histological and molecular analyses.

RESULTSSuccessful transgene expression was confirmed in the culture media of sFlt-1 transduced G-292 cells using ELISA, and with positive X-gal staining of the LacZ transduced cells. Noteworthy tumors were grown in all mice on the tibiae receiving G-292 cell inoculation, with clear detection on microCT images starting 2 weeks after inoculation. Over the time period, tumors derived from sFlt-1 transduced G-292 cells were distinctively smaller in size compared to the ones from wide-type G-292 and G-292-LacZ cells. Histology showed typical osteosarcoma characteristics including severe cellular pleomorphism, bone erosions, and neo-vascularization. Real-time polymerase chain reaction indicated significantly higher sFlt-1 expression in sFlt-1 transduced groups than the wild-type G-292 or LacZ treated groups. Strong expression of oncogenes c-myc and c-fos were also obvious, along with the expression of VEGF in the primary tumor tissue.

CONCLUSIONRetrovirus-mediated sFLT-1 gene modification decelerates the osteosarcoma tumor growth in this murine model.

Animals ; Bone Neoplasms ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Female ; Genetic Vectors ; Humans ; Lac Operon ; Mice ; Mice, SCID ; Neovascularization, Pathologic ; metabolism ; pathology ; Osteosarcoma ; genetics ; metabolism ; pathology ; Retroviridae ; genetics ; Transgenes ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism

OBJECTIVETo evaluate the association between vasectomy and prostate cancer.

METHODSWe searched comprehensively the databases, CBMDisc, CMCC, CMAC, CNKI (from 1978 to January 6, 2009), and PubMed (from 1965 to January 6, 2009) using the key words "vasectomy" and "prostate cancer", screened the retrieved literature according to the inclusion and exclusion criteria, performed a Meta-analysis with the software RevMan 4.2 after identification of the relevant data, and calculated the overall pooled OR (95% CI) as well as that of the association of prostate cancer with <20 and > or =20 yr vasectomy.

RESULTSA total of 20 088 cases and 232 506 controls in 27 reports (7 cohort and 20 case-control studies) were included in this investigation. The overall pooled OR (95% CI) was 1.10 (0.97-1.24), and those of <20 and > or =20 yr vasectomy were 0.94 (0.83-1.06) and 1.05 (0.90-1.23), respectively.

CONCLUSIONNo existing literature show any positive association between vasectomy and prostate cancer.

Humans ; Male ; Prostatic Neoplasms ; epidemiology ; etiology ; Risk Factors ; Vasectomy ; adverse effects

OBJECTIVETo investigate the relationship of seminal plasma levocarnitine with sperm concentration, vitality and motility.

METHODSEnrolled in this study were 64 infertile men, who were divided according to the results of routine sperm tests into a normozoospermia (n = 12), an oligozoospermia (n = 16), an asthenozoospermia (n = 20) and an oligoasthenozoospermia group (n = 16). The level of seminal plasma levocarnitine was detected by LC-MS-MS, the concentration of seminal plasma testosterone measured by chemiluminescence immunoassay, the correlation of seminal plasma levocarnitine with sperm concentration, motility and vitality determined by bivariate correlation analysis with SPSS15.0, and so was the correlation between the carnitine and sperm concentration by partial correlation analysis with seminal plasma testosterone as a control variable to exclude the influence of testosterone.

RESULTSThe concentrations of total seminal plasma levocarnitine, free seminal plasma levocarnitine and seminal plasma acetolevocarnitine were (91.33 +/- 40.49) mg/L, (40.89 +/- 24.13) mg/L and (50.44 +/- 21.90) mg/L; the Pearson coefficients of correlation of the levocarnitine level with sperm motility, vitality and concentration were 0.161 (P = 0.235), 0.114 (P = 0.370) and 0.637 (P < 0.001), those of free seminal carnitine with sperm motility and vitality were 0.325 (P = 0.024) and 0.316 (P = 0.029), respectively, with the oligozoospermia group excluded, and that of partial correlation between the concentrations of seminal levocarnitine and sperm was 0.641 (P < 0.001).

CONCLUSIONThe level of seminal plasma levocarnitine is positively correlated with sperm motility and vitality, and more significantly with sperm concentration.

Adult ; Carnitine ; analysis ; Humans ; Infertility, Male ; physiopathology ; Male ; Semen ; chemistry ; cytology ; Sperm Count ; Sperm Motility ; physiology ; Spermatozoa ; cytology ; physiology ; Young Adult

OBJECTIVETo evaluate the clinical application of three-dimensional dynamic contrast-enhanced MR angiography (3D DCE MRA) in diagnosis of angiostenosis after liver transplantation.

METHODSTwenty recipients of liver transplantation underwent 3D DCE MRA examination. The blood vessel rating grades were accessed and the relative diameter of vascular anastomosis was measured; and the results were compared with those of US or DSA examination.

RESULTSSatisfactory angiography images were obtained in all cases by 3D DCE MRA, including 11 cases with normal and mild stenosis, 5 with moderate and 4 with severe stenosis in hepatic artery. Except one case in which 3D DCE MRA showed severe stenosis but DSA showed moderate stenosis, the results of MRA were all consistent with those of US or/and DSA in the stenosis degree of the portal vein, hepatic vein and the postcava.

CONCLUSION3D DCE MRA is an effective technique to evaluate the degree of angiostenosis after liver transplantation.

Adult ; Constriction, Pathologic ; diagnosis ; Contrast Media ; Female ; Hepatic Artery ; pathology ; Hepatic Veins ; pathology ; Humans ; Image Enhancement ; Imaging, Three-Dimensional ; Liver ; blood supply ; Liver Transplantation ; adverse effects ; Magnetic Resonance Angiography ; methods ; Male ; Middle Aged ; Portal Vein ; pathology

OBJECTIVETo explore the association between early menarche with anthropometry measurements among adolescent girls in China.

METHODSResearch material was selected from the data of 2010 Chinese National Surveys on Students Constitution and Health. Probability unit regression method was used to calculate the age of 10th percentile (P 10) at menarche and menarche age before the P 10 was defined as early menarche(9.0-11.6 years old). A total of 1072 girls with early menarche were screened. Each girl with early menarche was frequency matched with two girls who hadn't achieved menarche and with the age difference less than 0.1 yr and from the same urban or rural locations. A total of 2144 girls without menarche were screened. Participants' data of height, weight, sitting height, chest circumference, body mass index(BMI) and height and sitting height index were analyzed. t test and wilcoxon test were used to analyze the anthropometry measurements differences between the two groups, Chi square test was used to analyze the differences of overweight and obesity between the two groups. Multilevel model was used to explore the association between early menarche with anthropometry measurements and overweight and obesity.

RESULTSA total of 1072 girls with early menarche and 2144 girls without menarche. Early menarche girls' height, sitting height, chest circumference, weight and BMI were (151.42 ± 7.46) cm, (80.86 ± 4.21) cm, (73.88 ± 7.72) cm, (44.32 ± 9.35) kg, and (19.18 ± 3.03) kg/m(2), while they were (144.86 ± 7.55) cm, (76.96 ± 4.05) cm, (67.25 ± 6.94) cm, (36.07 ± 7.88) kg and (16.64 ± 2.48) kg/m(2) in girls without menarche. The difference between two groups were significant(Z values were -22.20, -23.69, -24.38, -23.12, -20.17, -6.33 respectively with all P values < 0.01). Multilevel analysis results showed that in 9.0-11.6 years old girls early menarche was associated with anthropometry measurements(all P values < 0.05). Compared with girls without menarche, girls with early menarche had a relative higher height, sitting height, weight, chest circumference, with increments of 5.28 cm, 3.37 cm, 5.53 cm, 6.37 kg, 1.79 kg/m(2). Within subgroup analysis, there were parabolic trends with age in the height, weight and sitting height differences and "U" trend in chest circumference difference between girls with early menarche and girls without menarche.In 9.0-10.8 years old, 10.9-11.0 years old and 11.1-11.2 years old groups, the risk of overweight and obesity among girls with early menarche were 2.98 (95%CI:1.92-4.63) times, 6.76 (95%CI:2.79-16.39) times, 2.99 (95%CI:1.40-6.40) times of girls without menarche.

CONCLUSIONThe early onset of menarche is related with height, sitting height, weight and chest circumference, and it is closely associated with overweight and obesity among adolescent girls in China.

Body Mass Index ; Child ; Child Development ; China ; epidemiology ; Female ; Humans ; Menarche ; Overweight ; epidemiology ; Pediatric Obesity ; epidemiology