Excessive bile acid activated NF-kappa B and promoted the development of alcoholic steatohepatitis in farnesoid X receptor deficient mice.

Chronic and excessive alcohol consumption can lead to alcoholic liver disease (ALD), which is characterized by a spectrum of liver disorders, including fatty liver, alcoholic steatohepatitis (ASH), fibrosis/cirrhosis and hepatocellular carcinoma (HCC). The mechanism of the progression from alcoholic steatosis to steatohepatitis and fibrosis is still not fully understood. As a nuclear receptor, farnesoid X receptor (FXR) plays a critical role in maintaining hepatic lipid and bile acid homeostasis. To clarify the role of FXR in the progression of steatohepatitis, we studied the effect of ethanol feeding on FXR-deficient mice. Wild-type and FXR-deficient mice were fed with Lieber-DeCarli ethanol liquid diet or an isocaloric control diet. We found that FXR-deficient mice fed with ethanol diet developed more severe liver injury and steatosis, even progressed to steatohepatitis and moderate fibrosis. Whereas, wild-type (WT) mice only developed mild level of steatosis, with rarely observed inflammatory foci and collagen accumulation. We also found that ethanol induced hepatic bile acid accumulation and NF-κB activation in FXR-deficient mice, which could be attenuated by ursodeoxycholic acid (UDCA). Thus, FXR deficient mice were more prone to develop alcoholic steatohepatitis and fibrosis upon ethanol diet feeding. Our results highlight the role of FXR in hepatoprotection during ALD development. Moreover, attenuating alcoholic liver cholestasis would be beneficial in preventing the progression of hepatic hepatitis in patients with ALD.

[Study on subtype of human papillomavirus infection among aged 25 - 54 reproductive women in Beijing from 2006 to 2008].

OBJECTIVE: To investigate subtype of HPV infection among women at age of 25 to 54 years in Beijing. METHODS: From Sept. 2006 to Dec. 2008, 5552 reproductive women at age of 25 to 54 years classified into each 5-year as group were screened. Each participant completed a questionnaire and a sample of exfoliated cervical cells for liquid-based cytology and HPV subtype gene testing was performed. RESULTS: The overall prevalence of HPV was 6.68% (371/5552). High-risk HPV and Low-risk HPV prevalence were 5.76% (320/5552) and 2.00% (111/5552), respectively. The most common HPV types were HPV16 (2.61%, 145/5552), HPV58 (0.97%, 54/5552), HPV33 (0.85%, 47/5552), HPV43 (0.74%, 41/5552) and HPV56 (0.70%, 39/5552). There were two peaks of HPV prevalence: groups of 30 - 34 years and 40 - 44 years. CONCLUSION: The most common HPV subtypes in Beijing were HPV 16, 58, 33 and 43 and HPV prevalence showed a bi-modal age-specific curve.

[Analysis of high risk factors associated with cervical intraepithelial neoplasia in married women aged 25 - 54 years in Beijing between 2007 - 2008].

OBJECTIVE: to investigate high risk factors associated with cervical intraepithelial neoplasia (CIN) in married women aged 25 to 54 years in Beijing. METHODS: from Mar. 2007 to Sep. 2008, 6339 married women at age of 25 to 54 years were selected randomly by cross sectional survey in a total of 137 communities of 12 districts or counties in Beijing. The interview was carried out with unified questionnaires, gynecological examination. The cervical smear cytology and high-risk human papillomavirus (HR-HPV) infection of cervical secretion were detected. Women with abnormal cervical cytology underwent colposcopy and cervical biopsy. Odd ratio (OR) and 95% confidence interval (CI) of related high risk factors with CIN were studied by logistic regression analysis. RESULTS: among 6339 women, the prevalence rate of CIN including 4 squamous cell carcinoma (SCC) was 5.90% (374/6339). By multinomial regression analysis, HR-HPV infection (95%CI: 9.953 - 15.811), History of trichomonas vaginitis (95%CI: 1.046 - 2.104), oral contraceptives (95%CI: 1.087 - 1.806), age less than 45 years old (95%CI: 1.069 - 1.828) were related with CIN. CONCLUSION: infection rate of HR-HPV is an independent risk factor of CIN, however, the history of trichomonas vaginitis, oral contraceptives and age less than 45 years old are related risk factors of CIN.

[Epidemiological study on the prevalence of cervical intraepithelial neoplasia among married women aged 25-54 years in Beijing between 2007-2008].

OBJECTIVE: To investigate prevalence of cervical intraepithelial neoplasia (CIN) among the married women aged 25-54 years in Beijing. METHODS: With method of cross sectional survey, 6339 married women at age of 25 to 54 years were selected randomly in 137 communities of 12 districts or counties in Beijing from March 2007 to September 2008. The cervical smear cytology and high-risk human papillomavirus (HPV) infection of cervical secretion were detected. Women with abnormal cervical cytology were underwent colposcopy and cervical biopsy. RESULTS: Among 6339 women, 9.58% (607/6339) cases had abnormal cytological results, the colposcopy and cervical biopsy showed the rate of CIN was 5.84% (370/6339) in total selected women and 60.96% (370/607) in women with abnormal cervical cytology, including 4.65%(295/6339) in CIN I, 0.80% (51/6339) in CIN II, 0.38% (24/6339) in CIN III; 0.06% (4/6339) in early invasive carcinoma (SCC). Based on geographical distribution, the rate of cervical lesions was 4.46% (42/942) in urban areas, 6.27% (188/3000) in suburbs and 6.01% (144/2397) in outer suburbs (P > 0.05). CONCLUSION: It was found that the incidence of CIN was 5.84% in married women aged 25-54 years in Beijing, which did not show significant prevalence in urban, suburb and outer suburbs region.

[Analysis of correlation factors for cervical intraepithelial neoplasia in married women in Beijing, China].

OBJECTIVE: To investigate the characteristic of precancerous conditions of cervical intraepithelial neoplasia (CIN) and its related high-risk factors among the married women in Beijing, China. METHODS: Based upon the method of cross-sectional survey, 6339 married women at reproductive age from 25 to 54 years old were selected randomly in a total of 137 communities of 12 districts or counties in Beijing from March 2007 to September 2008. The interview was carried out with unified questionnaires and gynecological examinations. And the cervical Pap smear was used for liquid-based cytological examination and the cervical secretion for detection of high-risk human papillomavirus (HPV) DNA. Furthermore, the women with abnormal cervical cytology received colposcopy and cervical biopsy. RESULTS: (1) Among 6, 339 study subjects, 374 cases had CIN and the prevalence rate was 5.9%; (2) For the cases with cervical cytology positive results, cervical biopsy showed an elevated level of abnormal cytology and an increased incidence of cervical lesions; (3) The peak age of CIN prevalence was 30 to 34 years old and there was a high grade of cervical neoplasia; (4) Among the population, the infection rate of high-risk HPV was 9.9% and the infection rate of high-risk HPV in positive cytological group (41.2%) was significantly higher than that in negative cytological group (6.6%); (5) The infection rate and DNA load of high-risk HPV increased following the severity grade of CIN. CONCLUSION: In Beijing, married women at 30 to 34 years old are the high-risk group in CIN incidence and the infection of high-risk HPV is an independent risk factor. Liquid-base cytology combined with high-risk HPV DNA test is a viable method to discover CIN in time and prevent the incidence of cervical cancer.

[Study on the relations between high risk human papillomavirus and cervical intraepithelial neoplasia in married women from Beijing].

OBJECTIVE: To investigate the prevalence and relationship between high risk human papillomavirus (HR-HPV) and cervical intraepithelial neoplasia (CIN) in married women from Beijing. METHODS: From March 2007 to September 2008, a total of 6185 married women were sampled, covering 137 communities in 12 districts. The samples were screened by high-risk HPV DNA test (HC2) and cytological test. For those participants with cytological test results ≥ ASCUS, pathological tests were performed. An interview was also carried out with the same questionnaire. Results from the tests were inputted into the database twice using EpiData 3.0, reviewed, analyzed, using SPSS 15.0. RESULTS: (1) The prevalence rates of HR-HPV and CIN were 9.9% and 6.0%, respectively for the age group 25 to 54. (2) The peak age groups for HR-HPV and CIN prevalence rates were 30 to 34 years old. (3) The prevalence rates of positive cytology (40.3%) and CIN (30.4%) in HR-HPV positive female population were significantly higher than that in HR-HPV negative group. (4) Data from unconditional logistic regression analysis showed that, when comparing with the normal subjects, the risk odds ratios of HR-HPV with low grade CIN and cervical cancer/high grade CIN were 8.385 and 97.416 and the attributable risk proportions with these groups were 88.1% and 99.0%, respectively. CONCLUSION: HR-HPV infection seemed to be the main risk factor for CIN. Married women, from age group 30 - 34, were under the high risk group in both HR-HPV infection and CIN incidence.

[Prevalence and determinants of lower reproductive tract infections among women aged 25 - 54 years in Beijing].

OBJECTIVE: To determine the prevalence and determinants of the most commonly seen lower reproductive tract infections among women aged 25 - 54 years in Beijing. METHODS: The study population consisted of 6339 women aged 25 - 54 years in 137 communities of Beijing. Focus of this study was to understand the prevalence of the following diseases as:bacterial vaginosis, trichomoniasis and vulvovaginal candidiasis. In addition to their prevalence rates, a generalized equation for estimation was used to analyze those infection-associated factors. RESULTS: The overall infection prevalence in the lower reproductive tract was 11.4%, including bacterial vaginitis as 8.7%, trichomonads as 1.0% and vulvovaginal candidiasis as 1.7%. Factors which were found to be significantly associated with lower reproductive tract infections in women were age, profession, family income, number of sex partners and frequency of condom use during sexual contacts. In patients with bacterial vaginitis, both prevalence rates of cervical intraepithelial neoplasia and infection of human papillomavirus were high. CONCLUSION: The prevalence of the most commonly seen lower reproductive tract infections among women aged 25 - 54 years in Beijing was lower than other areas in China. Lower reproductive tract infections seemed to be related to 30 - 49 years of age, nongovernmental employee, poverty, higher number of sex partners and not using condoms during sexual contacts.

[Epidemiological study of high risk human papillomavirus infection in 25 to 54 years old married women in Beijing.].

OBJECTIVE: To investigate high risk human papillomavirus (HR-HPV) prevalence among married women in Beijing and to study the high risk factors. METHODS: During March 2007 to September 2008, a total of 6185 married women sampled from 137 communities in 12 districts were screened by HR-HPV DNA test and cytological test. The interview was carried out with unified questionnaires. The database was set up and twice entered in EpiData 3.0. After checked up, the data were analyzed in SPSS 15.0. RESULTS: (1) The HR-HPV infection rate was 9.89%. The HR-HPV infection rate of the city zone, the suburb and the exurb were 9.34%, 10.51% and 9.51% (P > 0.05). The HR-HPV infection rate of the native and the outlander were 9.53%, 11.30% (P < 0.05). (2) The age distribution of HR-HPV infection was that the rate was around 10% among 25 to 44 age groups, which was the highest (11.21%) in 30 to 34 age group; then the rate was descended as the age raising, the rate of 50 to 54 age group was the lowest (7.78%). (3) Multiple logistic regression showed that the related risk factors of HR-HPV infection mainly included 1000 RMB and above of family income per person per month, possessing more than 1 sexual partner of her husband, outlander and high levels of education. (4) The prevalence of cervical intraepithelial neoplasia (CIN) in HR-HPV positive group was significantly higher than that in HR-HPV negative group (29.76% vs 3.32%, P < 0.01). CONCLUSIONS: (1) The HR-HPV infection rate among aged 25 to 54 years was 9.9% and there was no significant difference in area distribution. (2) The high risk population which should strengthen screening was the married bearing-age women with high level of family income, outlander, high levels of education and her husband possessing more than 1 sexual partner. (3) HR-HPV infection is the main risk factor for CIN and cervical cancer, while does not provide a causal relationship with them. The high risk population should be checked regularly to understand the development of HR-HPV infection and CIN incidence.

Involvement of beta 1,4 galactosyltransferase 1 and Gal beta1-->4GlcNAc groups in human hepatocarcinoma cell apoptosis.

Beta 1,4 galactosyltransferase 1 (beta 1,4GT1) synthesizes Gal beta 1-->4GlcNAc groups in N-linked sugar chains of animal glycoproteins, which have been demonstrated to play an important role in many biological events, including sperm-egg interaction, cell migration and mammalian embryonic development. In this study, the mRNA level of beta 1,4GT1 was found to increase greatly during the 7721 hepatocarcinoma cells apoptosis induced by cycloheximide. Ricinus Communis Agglutinin-I staining indicated generous increase of Gal beta 1-->4GlcNAc groups during apoptosis. Further study showed that the 7721 hepatocarcinoma cells transiently transfected with beta 1,4GT1 were more susceptible to the apoptosis induced by cycloheximide. The increased susceptibility was in accordance to the transfection concentration of beta 1,4GT1, which also led to the increased Gal beta 1-->4GlcNAc groups on the transfected cell surface. All the observations suggested that beta 1,4GT1 and Gal beta 1-->4GlcNAc groups might be associated with the apoptosis of human hepatocarcinoma cells.