Yunhai Liu

Incidence of Cerebral Hemorrhage in the Changsha Community

Background and Purpose: Intracranial hemorrhage (ICH) constitutes an important subtype of stroke. In a prior study, we found that the city of Changsha, People’s Republic of China, not only had a high incidence of stroke, but also had almost the highest incidence of cerebral hemorrhage. To provide information for preventing and managing ICH, we undertook this study supervising and determining the annual first-ever average incidence of cerebral hemorrhage from 1986 to 2000 in Changsha. Methods: In January 1986, people from 6 well-defined communes in the Kai-fu district in Changsha were selected as the study population. Since 1991, we added another 18 well-defined communes of the same district. Data on these residents were obtained from the census register of the local administrative office. Persons who had a history of stroke were excluded from our study at the beginning. Every year, we checked up on the population and carried out door-to-door inquiries to verify the new cases of ICH and stroke. If the patients were diagnosed in hospital, as many as possible were examined with CT and/or MRI. The incidence rate adjusted to the World population in 1985 for age and sex, as well as the prevalence of risk factors were calculated. Results: An accumulative total of 551,163 people were supervised in 15 years (from 1986 to 2000); the annual average incidences of stroke and ICH were 236.6/100,000 (adjusted rate: 154.7) and 131.0/100,000 (adjusted rate: 73.1), respectively. From 1986 to 2000, the total annual average rate of stroke confirmed by CT and/or MRI in Changsha was 70.8%, and for ICH it was 64.7%. The incidences of stroke and ICH confirmed by image analysis were 167.5 (adjusted rate: 110.8) and 84.7 (adjusted rate: 55.1), respectively. The mean annual mortality rate of ICH was 78.3/100,000 (adjusted rate: 49.3) and that of stroke was 124.5/100,000 (adjusted rate: 97.0). The percentage of ICH among stroke cases was 55.4%. Among patients with ICH, 79.8% had hypertension, 30.6% had cardiovascular disease, 7.6% had diabetes mellitus, and 12.5% had an abnormal high level of lipid. Among patients with other subtypes of stroke apart from ICH, the percentages were 76.6, 40.6, 15.5, and 22.5%. Conclusions: The incidence of ICH in Changsha is very high, so is the proportion of ICH among all stroke cases. Changsha is an area with a high incidence of ICH in the world. Hypertension is the prominent risk factor. The study demonstrated the importance of ICH as a significant subtype of stroke.

Human serum paraoxonase gene polymorphisms, Q192R and L55M, are not associated with the risk of cerebral infarction in Chinese Han population

Abstract Objectives: It has been reported that human serum paraoxonase (PON1) gene is associated with coronary heart disease (CHD) and diabetes mellitus (DM). However, little is known about the role of PON1 gene polymorphism in cerebral infarction (CI). For this, we have investigated the relationship between PON1 gene polymorphisms, Q192R and L55M, and CI in Chinese Han population. Methods: The PON1 genotypes, Q192R and L55M, from 153 CI patients and 153 healthy individuals, were determined by polymerase chain reaction (PCR) and restriction enzyme digestion. Their allele frequencies were then determined. The association of the PON1 gene polymorphism with the risk of CI was analysed by statistical analysis software. Results: The frequencies of PON1-Q192R genotypes in CI and control group are 13.7 and 9.8% (QQ), 51.6 and 53.6% (QR), 34.6 and 36.6% (RR) respectively. There is no significant difference in PON1-Q192R genotype (p=0.566) and allele frequencies (p=0.505) between CI patients and controls. The frequencies of PON1-55 genotypes in the CI and control group are 96.7 and 93.5% (LL), 3.3 and 6.5% (LM) respectively. No MM genotype was found in both CI and control group. No significant difference in genotype (p=0.289) and allele (p=0.296) distribution between CI patients and controls was observed. Discussion: Our results suggest that the human serum paraoxonase polymorphisms, Q192R and L55M, are not associated with the risk of cerebral infarction in Chinese Han population.

Involvement of Nuclear Factor κB (NF-κB) in the Downregulation of Cyclo-Oxygenase-2 (COX-2) by Genistein in Gastric Cancer Cells

Genistein induces growth inhibition in various human cancer cell lines but its mechanism of action remains unknown. This study determined whether the effect of genistein is mediated via suppression of cyclo-oxygenase (COX)-2 protein, and elucidated the mechanism of action of this effect in the human gastric cancer cell line BGC-823. Genistein treatment inhibited cell proliferation and induced apoptosis in a dose- and time-dependent manner; Western blotting analysis indicated a significant dose-dependent decrease in COX-2 protein levels. Genistein treatment exerted a significant inhibitory effect on activation of the transcription factor nuclear factor κB (NF-κB). Additionally, the NF-κB inhibitor pyrrolidine dithiocarbamate caused a reduction in COX-2 protein levels and NF-κB activation, similar to the effect of genistein. Suppression of COX-2 protein may be important for the antiproliferative and proapoptotic effects of genistein in BGC-823 cells, and these effects may be partly mediated through the NF-κB pathway.

Apolipoprotein H Gene Polymorphisms and Risk of Primary Cerebral Hemorrhage in a Chinese Population

Background and Purpose: Apolipoprotein H (ApoH) has been implicated in several physiologic pathways including lipid metabolism, coagulation and the production of hypertension, which are related to the pathogenesis of primary cerebral hemorrhage (PICH). The gene coding for ApoH is polymorphic, with the occurrence of several common alleles in the general population. This genetically determined variation can effect lipid metabolism and the production of hypertension. We determined the distribution of ApoH gene polymorphisms in Chinese people and investigated whether these polymorphisms were associated with increased risk of PICH in a Chinese population. Methods: We studied polymorphisms of the ApoH gene by the polymerase chain reaction-single strand conformation polymorphism technique and DNA sequencing in 140 PICH patients and 100 healthy control subjects. Serum antiphospholipid antibodies and lipid levels were also examined in all subjects. Results: Four polymorphisms of the ApoH gene have been identified in Chinese people. No difference in genotype frequencies of G817T (Leu247Val) polymorphism, G1025C (Try316Ser) polymorphism and C1080T polymorphism was observed between PICH patients and control subjects (p > 0.05). The G341A (Ser88Asn) polymorphism correlated significantly with PICH. The frequencies of the A allele were significantly higher in PICH patients than in controls, especially in PICH patients with hypertension and a family history of stroke. Conclusions: Our results suggest that the G341A (Ser88Asn) polymorphism might be associated with increased risk of PICH in a Chinese population. The association appeared to be mediated by the generation of hypertension.

Incidence and trends of stroke and its subtypes in Changsha, China from 2005 to 2011

During the 1990s no significant changes were found for the high incidence of ischemic stroke (IS) in Changsha, in contrast to the increase observed in Beijing and Shanghai. However, the epidemiological patterns of stroke may change with economic development. This study aimed to examine the characteristics of stroke incidence transition in Changsha from 2005 to 2011. In 2007 two communities with a registered population of about 100,000 were selected and data from stroke patients who presented between 2005 and 2007 were retrospectively collected from January to June 2008. From January to December 2007 a stroke surveillance network was established and stroke patients who presented between 2008 and 2011 were prospectively registered. From 2005 to 2011 the mean annual age-adjusted incidence of first-ever stroke was 168.5/100,000 (95% confidence interval [CI] 159.0-178.0/100,000), with 189.3/100,000 (95% CI 175.1-178.0/100,000) for men and 148.7/100,000 (95% CI 136.0-161.4/100,000) for women. The mean annual age-adjusted incidence of IS, intracranial hemorrhage and subarachnoid hemorrhage was 72.6/100,000 (95% CI 66.3-78.9/100,000), 85.1/100,000 (95% CI 78.3-91.9/100,000) and 9.4/100,000 (95% CI 7.1-11.7/100,000), respectively. During the study period, the age-adjusted incidence of stroke increased at an annual rate of 3.7% (p=0.001); at 4.2% for men (p=0.001) and 3.1% for women (p=0.026). The age-adjusted incidence of IS increased at an annual rate of 3.5% (p=0.003) but no significant changes were seen for hemorrhagic stroke. Characteristics of stroke incidence transition may reflect underlying changes in risk factors and there is an urgent need to identify these factors and launch appropriate public health campaigns.

Fibrinogen polymorphisms associated with sporadic cerebral hemorrhage in a Chinese population

Fibrinogen plays an important role in the intrinsic and extrinsic pathways of blood coagulation. This study investigated the association between common variants in the fibrinogen gene and the risk of developing sporadic cerebral hemorrhage (CH). We performed genotyping analyses for three single nucleotide polymorphisms (SNP) in the fibrinogen gene in a case-controlled study involving 195 patients with CH and 116 control participants; both groups were of southern Han-Chinese origin. Logistic regression analysis indicated that haplotypes ATA (rs1800790+rs1800787+rs6050), AA (rs1800790+rs6050) and TA (rs1800787+rs6050) could nearly double the risk of sporadic CH (odds ratio [OR]=1.738, 95% confidence interval [CI]: 1.103-2.740, p=0.017; adjusted OR=1.762, 95% CI: 1.042-2.982, p=0.035), although the three SNP were not associated with sporadic CH when analyzed separately. These findings indicate that rs1800790, rs1800787 and rs6050 polymorphisms may contribute to the etiology of sporadic CH in the Chinese population.

Absence of association between atherosclerotic cerebral infarction and TNFSF4/TNFRSF4 single nucleotide polymorphisms rs1234313, rs1234314 and rs17568 in a Chinese population

Objective To clarify the association between atherosclerotic cerebral infarction (ACI) and the single nucleotide polymorphisms (SNP) rs1234313 and rs1234314 (in TNFSF4) and rs17568 (in TNFRSF4). Methods Genomic DNA was extracted from peripheral blood of patients with ACI and healthy control subjects. The presence of carotid plaque was determined. Rs1234313, rs1234314 and rs17568 were characterized via SNP genotyping assay and verified by DNA sequencing. Results Genotype distributions were in Hardy–Weinberg equilibrium. There were no significant differences in the allele and genotype distributions of rs1234313, rs1234314 and rs17568 between patients with ACI (n = 450) and healthy control subjects (n = 378), or between patients with ACI and carotid plaque (n = 342) and controls. Conclusions There were no significant associations between rs1234313, rs1234314 and rs17568 and ACI risk in a Han Chinese population.

Effect of β-(3,4-dihydroxyphenyl)lactic acid on oxidative stress stimulated by high glucose levels in human peritoneal mesothelial cells.

OBJECTIVE: To investigate the effects of β-(3,4-dihydroxyphenyl)lactic acid on oxidative stress stimulated by high glucose levels in human peritoneal mesothelial cells (HPMCs) in vitro. METHODS: HPMCs were incubated with 100 mol/l glucose followed by 0.625 – 20 mg/ml β-(3,4-dihydroxyphenyl)lactic acid. Reactive oxygen species (ROS) were quantified by flow cytometry. Relative levels of fibronectin-1 (FN1), collagen-I α1 (COL1A1), endothelin-1 (EDN1) and haem oxygenase-1 (HMOX1) mRNA and protein were quantified by real-time reverse transcription—polymerase chain reaction and Western blotting, respectively. Absolute levels of FN1 and COLIA1 were quantified by enzyme-linked immunosorbent assay. RESULTS: β-(3,4-Dihydroxyphenyl)lactic acid significantly decreased ROS levels, and EDN1 mRNA and protein levels, in dose- and time-dependent manners. HMOX1 mRNA and protein levels were significantly increased by β-(3,4-dihydroxyphenyl)lactic acid in dose-dependent manners. COL1A1 and FN1 mRNA and protein levels were significantly decreased by β-(3,4-dihydroxyphenyl)lactic acid in dose- and time-dependent manners. CONCLUSIONS: β-(3,4-Dihydroxyphenyl)lactic acid inhibited oxidative stress and reversed increases in FN1 and COLIA1 induced by high glucose levels in HPMCs. This may contribute to a protective role in peritoneal fibrosis.

Association of protein Z and factor VII gene polymorphisms with risk of cerebral hemorrhage: a case–control and a family-based association study in a Chinese Han population

Protein Z (PZ) and factor (F) VII are two important factors in the clotting pathway which have similar structure, linked function and nearby gene sites. The aims of this study were to investigate whether the common variants of PZ and FVII genes are associated with the risk of cerebral hemorrhage (CH) and to explore the combined effects of PZ and FVII polymorphisms for CH risk. We performed genotyping analysis for two single-nucleotide polymorphisms (SNPs) of FVII (rs510317 and rs6046) and three SNPs of PZ (rs2273971, rs3024718 and rs3024731) both in a population-based case–control study and in a family-based association study. Case–control analysis found no evidence of significant association. But family-based association study revealed that the G allele of PZ rs2273971, and three haplotypes carrying the ‘G’ allele of PZ rs2273971: haplotype GA, CG and CGA of PZ and FVII genes, all had a significant effect on CH susceptibility (Z = 1.882, P = 0.049; Z = 1.922, P = 0.044; Z = 1.826, P = 0.047; Z = 1.977, P = 0.048, respectively). While, the A allele of PZ rs2273971, and four haplotypes carrying or crossing the ‘A’ allele of PZ rs2273971: haplotypes CA, ACAA, ACAT and ACAAT of PZ and FVII genes, may confer protection against CH (Z =−1.882, P = 0.049; Z =−2.000, P = 0.045; Z =−2.319, P = 0.020; Z =−2.002, P = 0.045; Z =−2.015, P = 0.043, respectively). This is a first family-based association study providing genetic evidences that PZ and FVII genes, especially PZ rs2273971 are involved in the development of CH in Han-Chinese families.

Incidence and survival of lacunar infarction in a southern Chinese population: A 7-year prospective study

Abstract Objective: Little attention has been paid to the epidemiological characteristics of lacunar infarction (LAC) in China before. This study aimed to examine the incidence and survival of LAC in a southern Chinese population. Methods: From 2004–2010 in Changsha, two communities with a registered population of ∼100 000 were selected and data from first-ever ischaemic stroke (IS) cases were prospectively collected. Then the epidemiological characteristics of LAC and non-LAC were evaluated. Results: During the study period, the age-standardized incidence increased at an annual rate of 0.7% (p < 0.001) for LAC and 2.0% (p < 0.001) for non-LAC. The mean annual age-standardized incidence of LAC and non-LAC was 28.2/100 000 and 45.0/100 000, respectively. Compared with non-LAC patients, the prevalence of hypertension, diabetes and hyperlipidemia was significantly higher in patients with LAC (p < 0.05). Although the 30-day fatality rate was significantly lower in patients with LAC than non-LAC (0.5% vs. 14.9%, p < 0.001), there was no significant difference in survival between the two groups (96.7% vs. 95.2%, p = 0.203) after excluding the patients who died within 1 year of stroke onset. Conclusion: LAC is a common stroke sub-type in southern China and the long-term prognosis is not benign.