CD38 is a multifunctional enzyme expressed in a variety of mammalian tissues, its catalytic activity was involved in a wide range of physiological processes. Based on the reported inhibitor of human CD38 NADase, 33 purine derivatives were designed and synthesized. The biological activity assay showed that compounds 20 and 38 exhibited almost the same extent of inhibitory activities on human CD38 NADase as the lead compound H2. The results also revealed that small substituents at C-6 of purine ring gave no obvious effect on inhibitory activity, but phenylpropionyl moiety at N-2 could affect the binding mode of the compound with CD38. This study provides a reliable basis for future rational design of inhibitors for CD38.
ADP-ribosyl Cyclase 1 ; antagonists & inhibitors ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; Humans ; Purines ; chemical synthesis ; chemistry

OBJECTIVETo explore the protective effects of insulin-like growth factor-1(IGF-1) on the survival and apoptosis of cortical neurons of neonatal rat under oxidative stress and its significance.

METHODPrimary cortical neurons from newborn rat were cultured and the oxidative stress model was established. Then cells were randomly divided into IGF-1 group and control group. The concentration of LDH in supernatant was detected. Cell survival was determined with MTT assay and the expression of active Caspase-3 was measured using Western Blotting.

RESULT(1) The values of LDH gradually decreased with the increasing IGF-1 added to the cells [(0.5065 ± 0.0064) to (0.435 ± 0.0065), (P < 0.01)], but when the concentration of IGF-1 reached a certain level (> 25 ng/ml), there were no longer obvious effects on the level of LDH [(0.42 ± 0.012) to (0.418 ± 0.0098), (P > 0.05)]; Western blot showed that the level of active Caspase-3 was significantly decreased after treatment with IGF-1 [(0.662 ± 0.033) to (0.199 ± 0.01), (P < 0.01)]. (2) Compared with control group, without or with low concentration of H2O2 (0 - 40 µM), the values of LDH and the expression of active Caspase-3 in IGF-1 group were significantly decreased[(1.518 ± 0.137) to (1.068 ± 0.067), (P < 0.05) and 0.850 ± 0.042 to 0.597 ± 0.03, P < 0.01, respectively] while the values of MTT obviously elevated [(0.773 ± 0.062) to (1.196 ± 0.057), (P < 0.05)]; but with higher concentration (≥ 60 µM) of H2O2, the values of LDH and MTT and the expression of active Caspase-3 in IGF-1 group all had no significant difference (P > 0.05). (3) When the concentration of H2O2 reached 60 µM and higher, whatever concentration of IGF-1 could not lower the level of LDH compared with control group [(2.376 ± 0.04) to (2.442 ± 0.046), (P > 0.05)].

CONCLUSIONSOxidative stress can induce IGF-1 resistance of cortical neurons in neonatal rat, and even increasing the concentration of IGF-1 can not restore their sensitivity to IGF-1.

Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Survival ; Cells, Cultured ; Hydrogen Peroxide ; administration & dosage ; pharmacology ; Insulin-Like Growth Factor I ; administration & dosage ; metabolism ; pharmacology ; L-Lactate Dehydrogenase ; metabolism ; Neurons ; drug effects ; metabolism ; Neuroprotective Agents ; administration & dosage ; pharmacology ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley

PURPOSE: This descriptive study was done to identify the relationship between health literacy and health status and to provide basic data for developing nursing interventions for Korean-Chinese elders living in Yanbian, China. METHODS: For data collection, intentional sampling of 300 elders was used. The questionnaire was composed of 5 items based on "Ministry of Health, the People's Republic of China (2008)" to measure health literacy, 33 health status items from the "Korean Health Status Measure for Elderly People" developed by Shin (2002), revised for use in China, and 9 general characteristics. Data were analyzed using SPSS Win 13.0 program. RESULTS: Total level of health literacy was relatively high (68.7%). Elders had high scores for taking medicines according to doctor's instruction, but lower ones for full comprehension through communication with doctors. Health status was high for emotional, physical, and social function in that order. There were significant differences between general characteristics and health status for gender, age, marital status, education, family, smoking, and alcohol consumption in that order. Results of multiple regression analysis for factors influencing health status showed that self-report health level was the most influential, followed by health literacy, age, gender. CONCLUSION: Health literacy is the main factor affecting health promotion among minority elders indicating a need to develop health promotion programs for elders who have low health literacy.
Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; *Attitude to Health ; China ; Demography ; Female ; Health Promotion ; *Health Status ; Humans ; Korea ; Male ; Minority Groups ; Questionnaires

OBJECTIVEUnderstand the public's current attitudes and knowledge about suicide and, thus, provide essential information to the development of targeted public education programs-important components of the suicide prevention effort.

METHODSSeventeen mental health professionals who were extensively trained in the methods of conducting focus groups used a pre-tested focus group outline on attitudes and knowledge about suicide to conduct 101 focus groups and 18 individual in-depth interviews with a total of 842 community respondents from 6 regions in northern China. The focus groups and in-depth interviews were audio-taped, transcribed and analyzed using the QSR Nvivo text analysis software.

RESULTSMost respondents believed that suicide was a greater problem in rural areas and among women and identified physical illnesses, economic problems and interpersonal conflicts (particularly family conflicts) as the main causes of suicide. Rural residents and women were believed to exhibit impulsive suicidal behavior because of their personal limitations and over-sensitiveness. Most thought that suicide was understandable and a small proportion felt that it was acceptable behavior in certain circumstances. Almost all felt that suicide resulted in the stigmatization and a loss of 'face' for the family. Most believed that one should show concern for persons who have suicidal behavior and their family members and expressed a willingness to have superficial social relationships with them but were unwilling to establish close personal relations with them. The vast majority believed that suicide was either very difficult or impossible to prevent.

CONCLUSIONSIn China the community is tolerant, sympathetic and, in some cases, accepting of suicide but there remains a substantial underlying stigmatization of suicide. Community members have some misunderstandings about suicide; the most obvious misunderstanding is the underestimation of the importance of mental illness as a cause of suicide. The content of public health messages used in suicide prevention programs should be developed by combining findings from both qualitative and quantitative research.

China ; Health Knowledge, Attitudes, Practice ; Humans ; Social Support ; Suicide ; prevention & control ; psychology ; Surveys and Questionnaires

OBJECTIVETo investigate the status of vaccination against hepatitis B among postgraduate students of medical institutions of higher education in Guangzhou.

METHODSHBsAg and anti-HBs in the serum samples from 1139 postgraduate students were detected by ELISA. Data on hepatitis B vaccine inoculation were investigated by using a questionnaire. Statistical analyses were performed by using SAS software.

RESULTSThe HBsAg positive rate among the 1139 postgraduate students was 2.90 percent. The HBsAg positive rates in hepatitis B vaccine inoculated (1.15 percent) and non- inoculated (21.69 percent) postgraduate students were significantly different (x2=119.11, P<0.0001). The positive rates of HBsAb between the two groups were also significantly different (x2=62.05, P<0.0001). Among the hepatitis B vaccine inoculated students, 17.31 percent were negative for HBsAb. The positive rate of HBsAb among those inoculated the vaccine within the past 3 years was higher than that among those inoculated the vaccine earlier (0-3 years vs. 4-6 year, P=0.0089) (0-3 years vs. 7-9 years, P=0.0172) (0-3 years vs. >9 years, P=0.0474). The positive rate of HBsAb among the students who received hepatitis B vaccine booster dose was higher than that of the students who did not receive any booster dose (P=0.0093).

CONCLUSIONWith the increase of ages, the effect of vaccination for hepatitis B decreased. Male populations may be more susceptible to hepatitis B virus than female. It is necessary to monitor HBsAb levels for those who were inoculated with HBV vaccine more than 3 years ago to give booster dose in time to prevent HBV infection.

Adult ; China ; Female ; Hepatitis B ; immunology ; prevention & control ; virology ; Hepatitis B Antibodies ; blood ; Hepatitis B Vaccines ; administration & dosage ; immunology ; Hepatitis B virus ; immunology ; Humans ; Male ; Middle Aged ; Students, Medical ; Surveys and Questionnaires ; Vaccination ; Young Adult

OBJECTIVETo investigate the expression and significance of Clusterin in normal prostate, benign prostate hyperplasia (BPH) and prostate cancer.

METHODSClusterin expression in samples of 12 normal prostate, 15 BPH, and 56 prostate cancer were studied by immunohistochemical stain.

RESULTSOf 83 cases, 67 are positive or weak positive (81%). The rate of positive or weak positive for normal prostate, BPH and prostate cancer was 17% (2/12), 73% (11/15), and 96% (54/56) respectively. The expression level of Clusterin in prostate cancer was much higher than in normal prostate (t = 8.82, P < 0.01). BPH (t = 7.63, P < 0.01) was related positively with pathological grade (r = 0.649, P < 0.01) and stage (r = 0.609, P < 0.01) of prostate cancer.

CONCLUSIONClusterin may play an important role in the biological characteristics of prostate cancer by the anti-apoptosis pathway.

Apoptosis ; Clusterin ; metabolism ; physiology ; Female ; Humans ; Immunohistochemistry ; Male ; Prostate ; metabolism ; Prostatic Hyperplasia ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology ; physiopathology

OBJECTIVETo explore the feasibility of applying autosomal single nucleotide polymorphisms (SNPs) on parentage testing.

METHODSAll SNP genotyping results of HapMap (r27) were downloaded from the website. With self-made computer programs, SNPs were extracted when their minor allele frequency (MAF) were ≥ 0.30 among all of the 11 HapMap populations. Ninety-six SNPs were chosen and integrated into the Illumina Goldengate bead arrays on the condition that no linkage disequilibrium was found between them. Three father-child-mother trios (9 samples in total) were tested with the arrays. Cumulative paternity index (CPI) was then calculated and compared with genotyping results using 15 short tandem repeats (STRs)(Identifiler(TM)).

RESULTSFamily 1 was found to have nine SNPs or seven STRs that did not conform to the Mendelian laws, Family 2 had 13 such SNPs or seven STRs, and Family 3 only had one such SNP but no STR. For Family 3, when all of the 96 SNPs were used in combine, the CPI was 1207, which had contrasted with the CPI by the 15 STRs, i.e., 355 869.

CONCLUSIONWhen applied to paternity testing, the paternity exclusion (PE) value for a SNP is usually less than 1/3 of that of a STR. The proportion of SNPs not comforming to the Mendelian laws for the tested SNPs may not be as high as that of inconsistent STRs over all tested STRs. Because of the low mutation rate of a SNP, the CPI will be greatly reduced even if one SNP did not conform to the Mendelian laws. Therefore, highly accurate testing methods are required to reduce artificial errors when applying SNPs for paternity testing.

Fathers ; Female ; Genetic Testing ; methods ; Genotype ; HapMap Project ; Humans ; Male ; Mothers ; Paternity ; Polymorphism, Single Nucleotide ; genetics

BACKGROUNDFamilial cerebral cavernous malformations (CCMs), characterized by hemorrhagic stroke, recurrent headache and epilepsy, are congenital vascular anomalies of the central nervous system. Familial CCMs is an autosomal dominant inherited disorder and three CCM genes have been identified. We report a Chinese family with CCMs and intend to explore clinical, pathological, magnetic resonance imaging (MRI) features and pathogenic gene mutation of this family.

METHODSTotally 25 family members underwent brain MRI examination and clinical check. Two patients with surgical indications had surgical treatment and the specimens were subjected to histopathological and microstructural examination. In addition, polymerase chain reaction (PCR) and direct sequencing were performed with genomic DNA extracted from 25 family members' blood samples for mutation detection.

RESULTSBrain MRI identified abnormal results in seven family members. All of them had multiple intracranial lesions and four cases had skin cavernous hemangioma. T2-weighted sequence showed that the lesions were typically characterized by an area of mixed signal intensity. Gradient-echo (GRE) sequence was more sensitive to find micro-cavernous hemangiomas. There was a wide range in the clinical manifestations as well as the age of onset in the family. The youngest patient was an 8-year-old boy with least intracranial lesions. Histopathological and microstructural examination showed that CCMs were typically discrete multi-sublobes of berry-like lesions, with hemorrhage in various stages of illness evolution. They were formed by abnormally enlarged sinusoids and the thin basement membranes. A novel T deletion mutation in exon 14 of CCM1 gene was identified by mutation detection in the seven patients. But unaffected members and healthy controls did not carry this mutation.

CONCLUSIONSThe clinical manifestations were heterogenic within this family. We identified a novel mutation (c.1396delT) was the disease-causing mutation for this family and extended the mutational spectrum of CCMs.

Adult ; Animals ; Female ; Hemangioma, Cavernous, Central Nervous System ; diagnosis ; genetics ; Humans ; KRIT1 Protein ; Magnetic Resonance Imaging ; Male ; Microtubule-Associated Proteins ; genetics ; Middle Aged ; Mutation ; Pedigree ; Proto-Oncogene Proteins ; genetics

Chronic inflammation is thought to be the leading cause of colorectal cancer, and interleukin-10 (IL10) has been identified as a potent immunomodulatory cytokine that regulates inflammatory responses in the gastrointestinal tract. Although several single nucleotide polymorphisms (SNPs) in IL10 have been associated with the risk of colorectal cancer, their prognostic significance has not been determined. Two hundred and eighty-two colorectal cancer patients were genotyped for two candidate cancer-associated SNPs in IL10. The associations of these SNPs with distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier analysis and Cox regression model. The minor homozygote GG genotype of IL10 rs3021094 was significantly associated with a 3.30-fold higher risk of death compared with the TT+TG genotypes (P=0.011). The patients with IL10 rs3021094 GG genotype also had a poorer overall survival in Kaplan-Meier analysis (log-rank P=0.007) and in multivariate Cox regression model (P=0.044) adjusting for age, gender, carcinoembryonic antigen levels, tumor differentiation, stage, lymphovascular invasion, and perineural invasion. In conclusion, our results suggest that IL10 rs3021094 might be a valuable prognostic biomarker for colorectal cancer patients.
Aged ; Alleles ; Carcinoembryonic Antigen/blood ; Cell Differentiation ; Colorectal Neoplasms/*genetics/mortality/pathology ; Female ; Genotype ; Homozygote ; Humans ; Interleukin-10/*genetics ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; *Polymorphism, Single Nucleotide ; Regression Analysis ; Tumor Markers, Biological/genetics

INTRODUCTIONStudies have suggested that women who present with non-ST-segment elevation myocardial infarction (NSTEMI) may differ in their clinical response to early invasive strategy compared to male patients. We examined the impact of gender difference in NSTEMI patients on outcomes following invasive versus conservative treatment.

MATERIALS AND METHODSPatients enrolled in our national myocardial infarction (MI) registry between January 2000 and September 2005 with diagnosis of NSTEMI were retrospectively analysed. The study endpoint was the occurrence of major adverse cardiac events (MACE) in the patients at 1 year.

RESULTSA total of 1353 patients (62.2% male) with NSTEMI were studied. The mean age of men was 62 +/- 14 versus 72 +/- 12 years in women in the cohort (P <0.001). The prevalence of hypertension and diabetes mellitus were significantly higher in women. Men were more likely to undergo revascularisation than women (OR, 2.97; 95% CI, 2.18-3.89, P <0.001). Among those who were revascularised, there was no gender difference in survival or recurrent MI rates during hospitalisation and at 1 year. Compared to medical therapy, percutaneous coronary intervention (PCI) was associated with a significant reduction in MACE in both women (OR, 0.44; 95% CI, 0.20-0.95) and men (OR, 0.40; 95% CI, 4.79-12.75). The most important predictor of MACE for females was diabetes mellitus (HR, 1.98; 95% CI, 1.17-3.33).

CONCLUSIONSThere is a gender-based difference in the rate of revascularisation among patients with NSTEMI. Women benefit from an invasive approach as much as men, despite their advanced age, with similar rates of mortality and recurrent MI at 1-year follow-up.

Adrenergic beta-Antagonists ; therapeutic use ; Aged ; Aged, 80 and over ; Angioplasty, Balloon, Coronary ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Electrocardiography ; Female ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; surgery ; Platelet Aggregation Inhibitors ; therapeutic use ; Practice Patterns, Physicians' ; Recurrence ; Sex Factors ; Survival Analysis