PLG inhibits Hippo signaling pathway through SRC in the hepatitis B virus-induced hepatocellular-carcinoma progression.

PURPOSE: Hepatitis B virus (HBV) infection is one main cause of hepatocellular carcinoma (HCC), but the mechanisms of pathogenesis still remain unclear. METHODS: We screened the 1351 differentially expressed genes related to HBV-induced HCC by bioinformatics analysis from databases and found that Plasminogen (PLG) may be a key gene in HBV-induced HCC progression. Then, we used a series of experiments in vivo and in vitro to explore the roles of PLG in HBV-HCC progression, such as qRT-PCR, western blot, ELISA, flow cytometry and TUNEL assay, subcutaneous xenografts and histopathological analysis to reveal the underlying mechanisms. RESULTS: PLG was over-expressed in HBV positive hepatocellular carcinoma tissues and cells. PLG silencing promoted HBV-HCC cell apoptosis in vitro and suppressed the growth of HBV-induced HCC xenografts in vivo both through inhibiting HBV replication. Then, GO and KEGG analysis of these differentially expressed genes revealed that the Hippo pathway was the key pathway involved in HBV-induced HCC, and SRC, a downstream target gene of PLG, was highly expressed in HBV-induced HCC and related to the Hippo pathway. Thus, we speculated that PLG promoted HBV-induced HCC progression through up-regulating and activating the expression of SRC and promoting Hippo signaling pathway function on HBV-HCC cell survival. CONCLUSION: Our study suggests PLG may be an activator of HBV-infected hepatocellular carcinoma development, as a novel prognostic biomarker and therapeutic target for HBV-HCC.

[The relationship between prepregnancy body mass index and the occurrence of pregnancy induced hypertension].

OBJECTIVE: To examine the relationship between prepregnancy body mass index (BMI) and the risk of pregnancy-induced hypertension (PIH) in Chinese population. METHODS: Data were collected in 6 counties/cities covered by Perinatal Health Care Surveillance System which was part of the Sino-American cooperative project on neural tube defects prevention established in 1992. The study population consisted of 83 159 women who attended premarital or preconception medical physical examination and delivered single live births with at least 20 gestational weeks from 1995 to 2000 in Jiaxing area. The Chi-square test was employed to test the difference in the rates of PIH among groups with different BMI. Multivariate logistic regression was conducted to examine the association between prepregnancy BMI and the risk of PIH. RESULTS: The rate of PIH was 11.01% (9153/83 159; 95% CI: 10.79% - 11.22%). The rate of PIH among women with BMI < 18.5 kg/m(2), 18.5 - 22.9 kg/m(2), 23.0 - 24.9 kg/m(2), and > or = 25.0 kg/m(2) were 9.08% (1405/15 472; 95% CI: 8.63% - 9.54%), 10.82% (6389/59 054; 95% CI: 10.57% - 11.07%), 14.63% (943/6444; 95% CI: 13.78% - 15.52%), and 19.00% (416/2189; 95% CI: 17.38% - 20.71%), respectively, the difference was significant (chi(trend)(2) = 261.028, P = 0.000). Taking those with BMI 18.5 - 22.9 kg/m(2) as reference, the unadjusted RR for PIH was 0.82 (95% CI: 0.77 - 0.87) among women with BMI < 18.5 kg/m(2), 1.41 (95% CI: 1.31 - 1.52) among women with BMI 23.0 - 24.9 kg/m(2), and 1.93 (95% CI: 1.73 - 2.16) among women with BMI > or = 25.0 kg/m(2). After controlling for area, maternal age at delivery, educational level, occupation, parity, times of prenatal visit as well as the individual or family history of chronic hypertension, the estimated RR were 0.85 (95% CI: 0.80 - 0.90), 1.37 (95% CI: 1.27 - 1.47) and 1.88 (95% CI: 1.68 - 2.10), respectively. CONCLUSION: High prepregnancy BMI could increase the risk of PIH.

[Relations between pre-pregnancy body mass index, gestational weight gain, and the occurrence of neonatal asphyxia].

OBJECTIVE: To assess the relationship between pre-pregnancy body mass index (BMI), weight gain during pregnancy, and the risk of neonatal asphyxia. METHODS: Data was collected in 6 countiedeities covered by Peri-natal Health Care Surveillance System which was part of a Sino-American cooperative project on neural tube defects prevention established in 1992. The study population consisted of 83,030 women who attended premarital/preconception medical physical examination program and had delivered single live birth with at least 20 gestational weeks from 1995 to 2000 in Jiaxing area, Zhejiang province. RESULTS: from the Chi-square test were employed to test the differences in the rates of neonatal asphyxia between groups with different BMI and other characteristics. Multivariate logistic regression method was conducted to examine the association between pre-pregnancy BMI, gestational weight gain, and the risk of asphyxia. Results The average rate of neonatal asphyxia was 11.3% (95% CI: 11.1%-11.6%). The rates of neonatal asphyxia among women with BMI < 18.5 kg/m2, 18.5-22.9 kg/m2, 23.0-24.9 kg/m2, and > or = 25.0 kg/m2 were 11.0% (95% CI: 10.5%-11.5%), 11.3% (95% CI: 11.1%- 11.6%), 11.8% (95% CI: 11.0%-12.6%), and 12.9% (95% CI: 11.6%-14.4%) respectively. The rates of neonatal asphyxia were 12.4% among women with weight gain < 0.3 kg/wk, higher than women with higher weight gain. After adjusting for residential area, maternal age, educational level, occupation, parity, times of prenatal visit, high-risk experiences during pregnancy, high-risk experiences at time of delivery, gestational week and birth weight, the estimated ORs were 1.03 (95% CI: 0.97-1.09), 1.06 (95% CI: 0.96-1.16) and 1.14 (95% CI: 1.00-1.31), respectively. These ORs became 1.02 (95% CI: 0.95-1.09), 1.01 (95% CI:0.90-1.13) and 1.08 (95% CI: 0.92-1.28) after further adjusting the variable "gestational weight gain". The estimated ORs for neonatal asphyxia were 1.06 (95% CI: 1.01-1.12) for women with weight gain at 0.3-kg/wk and 1.09 (95% CI: 1.02-1.20) for women with weight gain <0.3 kg/wk when compared to those with weight gain > or = 0.5 kg/wk. CONCLUSION: Lower weight gain seemed to have the effect of increasing the risk of neonatal asphyxia.

[Study on the descriptive epidemiology of pregnancy-induced hypertension from 1995 - 2000 in Jiaxing of Zhejiang province, China].

OBJECTIVE: To describe the epidemiological characters of pregnancy-induced hypertension (PIH) in Jiaxing areas of Zhejiang province of China between 1995 and 2000. METHODS: We analyzed the perinatal health surveillance data that was collected as part of the Sino-American cooperative project on neural tube defects prevention established in 1992. The study population consisted of 136 070 pregnant women with at least 20 weeks of gestational age. National diagnostic criteria were used to identify the cases which were divided into three subgroups: mild, moderate and severe. RESULTS: 15 127 cases were identified and the overall incidence rate of PIH was 11.1% (95% CI : 11.0% - 11.3%). Among all the cases, mild, moderate and severe PIH were accounted for 71.4%, 22.3% and 6.3%, respectively. The proportions of PIH cases that occurred in the second trimester, third trimester and during delivery appeared to be 4.2%, 34.4% and 61.4%, respectively. There was a significant fall in the trend of PIH occurrence every year, which dropped from 10.7% in 1995 to 8.6% in 2000 by 19.6%. More risk of PIH seemed to be related to those mothers living in the urban areas with age under 20 or above 35, being peasants and having little educational, having had multiple gestations, conceiving in spring/summer or delivering in winter or spring etc. Compared with the results of national survey in 1988, the incidence rate of PIH was higher by 18.1%, while the proportion of severe PIH was much lower by 68.8%. Although the incidence rates of PIH in urban and rural areas were somehow similar, the proportion of severe PIH in rural areas was much higher than that in urban areas. CONCLUSION: Overall incidence rate and distribution of PIH were reported. Compared with the results in 1988, incidence rate of PIH was much higher, particularly for mild cases.

[Study on reduced folate carrier gene (RFC1) polymorphism in the southern and northern Chinese population].

OBJECTIVE: To describe the distribution of reduced folate carrier gene (RFC1)genotype and allele frequency between southern and northern, female and male Chinese population. METHOD: RFC1 (A80G) genotype was detected, using polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) on 720 blood spot DNA from the normal subjects. RESULTS: The frequencies of the northern population with AA, GG and GA genotypes were 22.28%, 31.09% and 46.63%, and the frequencies of the southern population were 18.56%, 22.75% and 58.68%, respectively. Findings showed that there were significant differences between southerners and northerners in RFC1 (A80G) genotype (P < 0.01). There was no significant difference between G allele frequency of the northern (52.10%) and southern population (54.40%). The frequencies of male with RFC1 (A80G) AA, GG and GA genotype were 24.88%, 25.85% and 49.27%, and among female were 18.83%, 27.77% and 53.40%, respectively. There were no significant differences between male and female in RFC1 genotype (P > 0.05), or between G allele frequency in female (50.49%) and that in male (54.47%). CONCLUSIONS: The distribution of RFC1 genotype seemed to be consistent with neural tube defects (NTDs) while its prevalence among the northerners was higher than that of southerners, with female having a higher NTDs prevalence. This study provided genetic epidemiological data for etiological hypothesis between RFC1 and diseases relative to folate metabolism.