Conservation and divergence of expression of GA2-oxidase homeologs in apple (Malus x domestica Borkh.).

In domesticated apple (Malus x domestica Borkh.) and other woody perennials, floral initiation can be repressed by gibberellins (GAs). The associated mechanism is a major unanswered question in plant physiology, and understanding organismal aspects of GA signaling in apple has important commercial applications. In plants, the major mechanism for elimination of GAs and resetting of GA signaling is through catabolism by GA2-oxidases (GA2ox). We found that the GA2ox gene family in apple comprises 16 genes representing eight, clearly defined homeologous pairs, which were named as MdGA2ox1A/1B to MdGA2ox8A/8B. Expression of the genes was analyzed in the various structures of the spur, where flowers are initiated, as well as in various structures of seedlings over one diurnal cycle and in response to water-deficit and salt stress. Among the results, we found that MdGA2ox2A/2B dominated expression in the shoot apex and were strongly upregulated in the apex after treatment with exogenous GA3, suggesting potential involvement in repression of flowering. Several MdGA2ox genes also showed preferential expression in the leaf petiole, fruit pedicel, and the seed coat of developing seeds, potentially representing mechanisms to limit diffusion of GAs across these structures. In all contexts studied, we documented both concerted and distinct expression of individual homeologs. This work introduces an accessible woody plant model for studies of GA signaling, GA2ox gene regulation, and conservation/divergence of expression of homeologous genes, and should find application in development of new cultivars of apple and other tree fruits.

Genetic mechanisms associated with floral initiation and the repressive effect of fruit on flowering in apple (Malus x domestica Borkh).

Many apple cultivars are subject to biennial fluctuations in flowering and fruiting. It is believed that this phenomenon is caused by a repressive effect of developing fruit on the initiation of flowers in the apex of proximal bourse shoots. However, the genetic pathways of floral initiation are incompletely described in apple, and the biological nature of floral repression by fruit is currently unknown. In this study, we characterized the transcriptional landscape of bourse shoot apices in the biennial cultivar, 'Honeycrisp', during the period of floral initiation, in trees bearing a high fruit load and in trees without fruit. Trees with high fruit load produced almost exclusively vegetative growth in the subsequent year, whereas the trees without fruit produced flowers on the majority of the potential flowering nodes. Using RNA-based sequence data, we documented gene expression at high resolution, identifying >11,000 transcripts that had not been previously annotated, and characterized expression profiles associated with vegetative growth and flowering. We also conducted a census of genes related to known flowering genes, organized the phylogenetic and syntenic relationships of these genes, and compared expression among homeologs. Several genes closely related to AP1, FT, FUL, LFY, and SPLs were more strongly expressed in apices from non-bearing, floral-determined trees, consistent with their presumed floral-promotive roles. In contrast, a homolog of TFL1 exhibited strong and persistent up-regulation only in apices from bearing, vegetative-determined trees, suggesting a role in floral repression. Additionally, we identified four GIBBERELLIC ACID (GA) 2 OXIDASE genes that were expressed to relatively high levels in apices from bearing trees. These results define the flowering-related transcriptional landscape in apple, and strongly support previous studies implicating both gibberellins and TFL1 as key components in repression of flowering by fruit.

Genetic mechanisms in the repression of flowering by gibberellins in apple (Malus x domestica Borkh.).

BACKGROUND: Gibberellins (GAs) can have profound effects on growth and development in higher plants. In contrast to their flowering-promotive role in many well-studied plants, GAs can repress flowering in woody perennial plants such as apple (Malus x domestica Borkh.). Although this effect of GA on flowering is intriguing and has commercial importance, the genetic mechanisms linking GA perception with flowering have not been well described. RESULTS: Application of a mixture of bioactive GAs repressed flower formation without significant effect on node number or shoot elongation. Using Illumina-based transcriptional sequence data and a newly available, high-quality apple genome sequence, we generated transcript models for genes expressed in the shoot apex, and estimated their transcriptional response to GA. GA treatment resulted in downregulation of a diversity of genes participating in GA biosynthesis, and strong upregulation of the GA catabolic GA2 OXIDASE genes, consistent with GA feedback and feedforward regulation, respectively. We also observed strong downregulation of numerous genes encoding potential GA transporters and receptors. Additional GA-responsive genes included potential components of cytokinin (CK), abscisic acid (ABA), brassinosteroid, and auxin signaling pathways. Finally, we observed rapid and strong upregulation of both of two copies of a gene previously observed to inhibit flowering in apple, MdTFL1 (TERMINAL FLOWER 1). CONCLUSION: The rapid and robust upregulation of genes associated with GA catabolism in response to exogenous GA, combined with the decreased expression of GA biosynthetic genes, highlights GA feedforward and feedback regulation in the apple shoot apex. The finding that genes with potential roles in GA metabolism, transport and signaling are responsive to GA suggests GA homeostasis may be mediated at multiple levels in these tissues. The observation that TFL1-like genes are induced quickly in response to GA suggests they may be directly targeted by GA-responsive transcription factors, and offers a potential explanation for the flowering-inhibitory effects of GA in apple. These results provide a context for investigating factors that may transduce the GA signal in apple, and contribute to a preliminary genetic framework for the repression of flowering by GAs in a woody perennial plant.

Identification of TPS family members in apple (Malus x domestica Borkh.) and the effect of sucrose sprays on TPS expression and floral induction.

Trehalose (α-D-glucopyranosyl α-D-glucopyranoside) is a non-reducing disaccharide that serves as a carbon source and stress protectant in apple trees. Trehalose-6-phosphate (T6P) is the biosynthetic precursor of trehalose. It functions as a crucial signaling molecule involved in the regulation of floral induction, and is closely related to sucrose. Trehalose-6-phosphate synthase (TPS) family members are pivotal components of the T6P biosynthetic pathway. The present study identified 13 apple TPS family members and characterized their expression patterns in different tissues and in response to exogenous application of sucrose during floral induction. 'Fuji' apple trees were sprayed with sucrose prior to the onset of floral induction. Bud growth, flowering rate, and endogenous sugar levels were then monitored. The expression of genes associated with sucrose metabolism and flowering were also characterized by RT-quantitative PCR. Results revealed that sucrose applications significantly improved flower production and increased bud size and fresh weight, as well as the sucrose content in buds and leaves. Furthermore, the expression of MdTPS1, 2, 4, 10, and 11 was rapidly and significantly up-regulated in response to the sucrose treatments. In addition, the expression levels of flowering-related genes (e.g., SPL genes, FT1, and AP1) also increased in response to the sucrose sprays. In summary, apple TPS family members were identified that may influence the regulation of floral induction and other responses to sucrose. The relationship between sucrose and T6P or TPS during the regulation of floral induction in apple trees is discussed.

Effect of exogenous GA3 and its inhibitor paclobutrazol on floral formation, endogenous hormones, and flowering-associated genes in 'Fuji' apple (Malus domestica Borkh.).

Gibberellins (GAs) reduce apple (Malus domestica) flowering rates; however, the mechanism of their action is not fully understood. To gain a better insight into gibberellin-regulated flowering, here, 5 year-old 'Fuji' apple trees were used to explore the responses of hormones [GA1+3, GA4+7, indole-3-acetic acid (IAA), zeatin-riboside (ZR), and abscisic acid (ABA)], and gibberellin- and flowering-associated genes, to applications of gibberellin acid (GA3) and paclobutrazol (PAC). Results showed that GA3 relatively stimulated vegetative growth and delayed floral induction. Moreover, GA3 spraying significantly affected contents of all endogenous hormones and all the genes tested in at least one time points: the content of endogenous GAs was increased instantly and that of ZR was reduced at 44 days after fullbloom (DAF), which might constitute an unfavorable factor for flower formation; MdKO (ent-kaurene oxidase gene) and MdGA20ox (GA20 oxidase gene) were significantly repressed by a high level of GAs through the negative feedback regulation of GA; additionally, the MdSPLs (SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE) in this study were all significantly repressed by GA3 but promoted by PAC; the expression of MdFT1/2 (FLOWERING LOCUS T), MdSOC1 (SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1) and MdAP1 (APETALA1) in GA3-treated buds changed in the same way, and they were repressed at 44 DAF. We suppose that GA3 spraying disrupts the balance between ZR and GAs, and inhibits floral induction, probably by suppressing MdSPLs and the floral integrators in flower induction, which ultimately contributed to inhibiting flower formation.

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.

Genome-wide identification of vegetative phase transition-associated microRNAs and target predictions using degradome sequencing in Malus hupehensis.

BACKGROUND: A long juvenile period between germination and flowering is a common characteristic among fruit trees, including Malus hupehensis (Pamp.) Rehd., which is an apple rootstock widely used in China. microRNAs (miRNAs) play an important role in the regulation of phase transition and reproductive growth processes. RESULTS: M. hupehensis RNA libraries, one adult and one juvenile phase, were constructed using tree leaves and underwent high-throughput sequencing. We identified 42 known miRNA families and 172 novel miRNAs. We also identified 127 targets for 25 known miRNA families and 168 targets for 35 unique novel miRNAs using degradome sequencing. The identified miRNA targets were categorized into 58 biological processes, and the 123 targets of known miRNAs were associated with phase transition processes. The KEGG analysis revealed that these targets were involved in starch and sucrose metabolism, and plant hormone signal transduction. Expression profiling of miRNAs and their targets indicated multiple regulatory functions in the phase transition. The higher expression level of mdm-miR156 and lower expression level of mdm-miR172 in the juvenile phase leaves implied that these two small miRNAs regulated the phase transition. mdm-miR160 and miRNA393, which regulate genes involved in auxin signal transduction, could also be involved in controlling this process. The identification of known and novel miRNAs and their targets provides new information on this regulatory process in M. hupehensis, which will contribute to the understanding of miRNA functions during growth, phase transition and reproduction in woody fruit trees. CONCLUSIONS: The combination of sRNA and degradome sequencing can be used to better illustrate the profiling of hormone-regulated miRNAs and miRNA targets involving complex regulatory networks, which will contribute to the understanding of miRNA functions during growth, phase transition and reproductive growth in perennial woody fruit trees.

Increasing trend of prevalence of infertility in Beijing.

BACKGROUND: Infertility is one of the most important and underappreciated reproductive health problems in developing countries. However, epidemiological data in the Chinese population are still sparse. The aim of the present study was to determine the current prevalence and prevalence trend of infertility in Beijing, and to identify the risk factors associated with infertility. METHODS: This cross-sectional study was conducted in Beijing in 2012. A stratified cluster sampling method was used to select 12 448 couples of whom the female partners were born between 1955 and 1985. All subjects were interviewed face to face. Infertility was defined as the failure to achieve a clinical pregnancy after 12 months of regular unprotected sexual intercourse. RESULTS: Of the 12 448 couples, 12 342 (99.1%) answered the questions appropriately. The prevalence of infertility was 4.2% (3.1% as primary and 1.1% as secondary infertility). An increase in the prevalence of infertility according to the age of the female partner was found: 1.3% infertility for married females born in the 1950s and 11.4% for married females born in the 1980s. The increase was found in both urban and suburban areas. In addition, a Logistic regression showed that for the female partner, higher education levels, an older age at first marriage, adverse occupational conditions, mental labor and pre-pregnancy contraception after marriage were all significantly associated with a higher risk of infertility. CONCLUSION: The prevalence of infertility has increased significantly among couples in Beijing, possibly because of an interaction among multiple factors.

Identification of apolipoprotein D as a cardioprotective gene using a mouse model of lethal atherosclerotic coronary artery disease.

Mice with homozygous null mutations in the HDL receptor (scavenger receptor class B, type I, or SR-BI) and apolipoprotein E (apoE) genes [SR-BI/apoE double KO (SR-BI(-/-)/apoE(-/-) or dKO) mice] spontaneously develop occlusive, atherosclerotic coronary artery disease (CAD) and die prematurely (50% mortality at 42 d of age). Using microarray mRNA expression profiling, we identified genes whose expression in the hearts of dKO mice changed substantially during disease progression [at 21 d of age (no CAD), 31 d of age (small myocardial infarctions), and 43 d of age (extensive myocardial infarctions) vs. CAD-free SR-BI(+/-)/apoE(-/-) controls]. Expression of most genes that increased >sixfold in dKO hearts at 43 d also increased after coronary artery ligation. We examined the influence and potential mechanism of action of apolipoprotein D (apoD) whose expression in dKO hearts increased 80-fold by 43 d. Analysis of ischemia/reperfusion-induced myocardial infarction in both apoD KO mice and wild-type mice with abnormally high plasma levels of apoD (adenovirus-mediated hepatic overexpression) established that apoD reduces myocardial infarction. There was a correlation of apoD's ability to protect primary cultured rat cardiomyocytes from hypoxia/reoxygenation injury with its potent ability to inhibit oxidation in a standard antioxidation assay in vitro. We conclude that dKO mice represent a useful mouse model of CAD and apoD may be part of an intrinsic cardioprotective system, possibly as a consequence of its antioxidation activity.

Direct interaction between surface ß1,4-galactosyltransferase 1 and epidermal growth factor receptor (EGFR) inhibits EGFR activation in hepatocellular carcinoma.

Our previous studies showed that cell surface ß1,4-galactosyltransferase 1 (ß1,4GT1) negatively regulated cell survival through inhibition and modulation of the epidermal growth factor receptor (EGFR) signaling pathway in human hepatocellular carcinoma (HCC) SMMC-7721 cells. However, the underlying mechanism remains unclear. Here we demonstrated that ß1,4-galactosyltransferase 1 (ß1,4GT1) interacted with EGFR in vitro by GST pull-down analysis. Furthermore, we demonstrated that ß1,4GT1 bound to EGFR in vivo by co-immunoprecipitation and determined the co-localization of ß1,4GT1 and EGFR on the cell surface via confocal laser scanning microscopy analysis. Finally, using (125)I-EGF binding experiments and Western blot analysis, we found that overexpression of ß1,4GT1 inhibited (125)I-EGF binding to EGFR, and consequently reduced the levels of EGFR dimerization and phosphorylation. In contrast, RNAi-mediated knockdown of ß1,4GT1 increased the levels of EGFR dimerization and phosphorylation. These data suggest that cell surface ß1,4GT1 interacts with EGFR and inhibits EGFR activation.

Dietary manipulation and social isolation alter disease progression in a murine model of coronary heart disease.

BACKGROUND: Mice with a deficiency in the HDL receptor SR-BI and low expression of a modified apolipoprotein E gene (SR-BI KO/ApoeR61(h/h)) called 'HypoE' when fed an atherogenic, 'Paigen' diet develop occlusive, atherosclerotic coronary arterial disease (CHD), myocardial infarctions (MI), and heart dysfunction and die prematurely (50% mortality ~40 days after initiation of this diet). Because few murine models share with HypoE mice these cardinal, human-like, features of CHD, HypoE mice represent a novel, small animal, diet-inducible and genetically tractable model for CHD. To better describe the properties of this model, we have explored the effects of varying the composition and timing of administration of atherogenic diets, as well as social isolation vs. group housing, on these animals. METHODOLOGY/PRINCIPAL FINDINGS: HypoE mice were maintained on a standard lab chow diet (control) until two months of age. Subsequently they received one of three atherogenic diets (Paigen, Paigen without cholate, Western) or control diet for varying times and were housed in groups or singly, and we determined the plasma cholesterol levels, extent of cardiomegaly and/or survival. The rate of disease progression could be reduced by lowering the severity of the atherogenic diet and accelerated by social isolation. Disease could be induced by Paigen diets either containing or free of cholate. We also established conditions under which CHD could be initiated by an atherogenic diet and then subsequently, by replacing this diet with standard lab chow, hypercholesterolemia could be reduced and progression to early death prevented. CONCLUSIONS/SIGNIFICANCE: HypoE mice provide a powerful, surgery-free, diet-'titratable' small animal model that can be used to study the onset of recovery from occlusive, atherosclerotic CHD and heart failure due to MI. HypoE mice can be used for the analysis of the effects of environment (diet, social isolation) on a variety of features of cardiovascular disease.

Distribution of human papillomavirus genotype and cervical neoplasia among women with abnormal cytology in Beijing, China.

OBJECTIVE: To understand the relationship between human papillomavirus (HPV) genotype distribution and cervical neoplasia among women with abnormal cytology in Beijing. METHODS: In a study in Beijing, China, participants underwent a gynecologic examination between September 2006 and December 2009. Those with abnormal cytology underwent colposcopy, biopsy, and HPV testing. HPV was typed by flow-through hybridization on formalin-fixed paraffin-embedded tissue. RESULTS: Among 6339 women examined, 533 with abnormal cytology underwent HPV testing. The prevalence of high-risk HPV (HR-HPV) subtypes was 29.8%. HPV-16 was the most common genotype (12.8%), followed by HPV-33, HPV-58, HPV-66, HPV-18, and HPV-52. The cytologic and histopathologic grade clearly increased with a higher prevalence of HR-HPV infection. Both HPV-16 and HPV-33 were significantly associated with grade CIN2+ lesions (P<0.05). By contrast, HPV-18 and HPV-66 were not associated with cervical lesion severity. HR-HPV infection was most common among women aged 30-34 years (35.0%). CONCLUSION: HPV-16, HPV-58, HPV-33, HPV-66, HPV-18, and HPV-52 were the most common genotypes in Beijing. HPV-16 and HPV-33 might be associated with CIN2+ lesions. HPV-18 and HPV-66 were not associated with high-grade cervical lesions. The present results might help to improve HPV vaccination and cervical cancer prevention programs in Beijing.

Fibroblast growth factor 7 inhibits cholesterol 7α-hydroxylase gene expression in hepatocytes.

Cholesterol 7α-hydroxylase (CYP7A1) is the initial and rate-limiting enzyme for bile acid synthesis. Transcription of the CYP7A1 gene is regulated by bile acids, nuclear receptors and cytokines. Fibroblast growth factor 7 (FGF7) secreted from activated hepatic stellate cells (HSC) during chronic liver fibrosis regulates hepatocyte survival and liver regeneration. In the carbon tetrachloride (CCl(4))-induced fibrotic mouse liver, we demonstrated that the expression of CYP7A1 was largely decreased while the expression of FGF7 was significantly increased. We further demonstrated that FGF7 inhibited CYP7A1 gene expression in hepatocytes. Knockdown study by short interfering RNA, kinase inhibition and phosphorylation assays revealed that the suppression of CYP7A1 expression by FGF7 was mediated by FGFR2 and its downstream JNK signaling cascade. The FGF7 neutralizing antibody restored CYP7A1 expression in Hep3B cells treated with conditioned medium from HSC. In summary, the data suggest that FGF7 is a novel regulator of CYP7A1 expression in hepatocytes and may prevent hepatocytes from accumulating toxic bile acids during liver injury and fibrosis.

Trihydrophobin 1 phosphorylation by c-Src regulates MAPK/ERK signaling and cell migration.

c-Src activates Ras-MAPK/ERK signaling pathway and regulates cell migration, while trihydrophobin 1 (TH1) inhibits MAPK/ERK activation and cell migration through interaction with A-Raf and PAK1 and inhibiting their kinase activities. Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1. Further study reveals that Tyr-6 phosphorylation of TH1 reduces its inhibition on MAPK/ERK signaling, enhances c-Src mediated cell migration. Moreover, induced tyrosine phosphorylation of TH1 has been found by EGF and estrogen treatments. Taken together, our findings demonstrate a novel mechanism for the comprehensive regulation of Ras/Raf/MEK/ERK signaling and cell migration involving tyrosine phosphorylation of TH1 by c-Src.

Prevalence of cervical intraepithelial neoplasia in patients with atypical squamous cells of undetermined significance from cervical pap smears in Beijing.

OBJECTIVES: To determine the prevalence and factors associated with histologic diagnoses of cervical intraepithelial neoplasia in women with ASC-US. METHOD: Sampling investigations were carried out on married women aged 25-54 in 12 districts in Beijing from April 2007 to November 2008. Further examinations and analyses were carried out on women with ASC-US in the cytological screening. RESULTS: Of 6,339 women, 9.6% suffered from cervical abnormalities in cytology; among them, 409 cases were ASC-US. Of the 409 ASC-US, 42.1% showed inflammation; 50.9% had CIN 1, 6.1% had CIN 2, and three cases had CIN 3, one of which was cervical cancer. Four hundred and four cases were subjected to detection for the human papillomaovirus (HPV) and the infection rate was 30.7%. Morbidity in the HPV infected patients that suffered from CIN 2 or higher was significantly higher than that in the uninfected population (chi2 = 26.685, p = 0.000). No statistical significance was found in the correlation between the pathological results of ASC-US and the loading dose of HPV infection (chi2 = 7.754, p = 0.458). CONCLUSION: The morbidity of CIN in women with ASCUS in Beijing is high, and women with ASC-US should be paid great attention, especially women who are infected with high-risk HPV.

Knowledge of cervical cancer among 25-54-year-old women in Beijing.

The purpose of this study is to examine knowledge of cervical cancer and the relationship between knowledge of human papillomavirus (HPV) infection and cervical disease in a largely representative Beijing population. A questionnaire-based survey was conducted in a Beijing population sample of married women ages 25 to 54 years (n = 6,339), evaluating knowledge and relevant factors with regard to cervical cancer. Knowledge levels were low; only 52.5% (n = 3,328) of the respondents knew that cervical cancer can be detected in its early stage. Only 26.9% reported that human HPV infections were risk factors for cervical cancer. The level of knowledge was lower among older, with less education, less income, unstable profession, and non-Beijing Hukou women (all P < 0.01). An increasing level of knowledge may impact positively on intentions to participate in cervical cancer screening. Education schemes to improve knowledge of cervical cancer should be performed in a multimodel, multichannel method.

[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.

A population-based study on the risks of cervical lesion and human papillomavirus infection among women in Beijing, People's Republic of China.

BACKGROUND: Few population-based studies have investigated premalignant and malignant cervical abnormalities in Beijing. METHODS: A total of 6,385 randomly selected sexually active women were interviewed and examined. Cervical lesion was diagnosed using cytology and histology. High-risk human papillomavirus (HPV) was detected by the second-generation hybrid capture test and typed by gene chip of DNA from paraffin-embedded tissue. RESULTS: The cervical lesion prevalence diagnosed by histology was 5.8%. High-risk HPV overall prevalence was 9.9%, 50.5% with cervical lesion and 7.4% without cervical lesion. High-risk HPV DNA load increased with increasing degree of lesions. HPV 16 was the most common type (26.5%) among women with cervical lesion, followed by HPV 58 (8.8%), HPV 33 (7.8%), and HPV 56 (5.3%). Women under 50 years of age, married status, pregnancy and delivery status, couple's sexual behavior, contraceptive history, columnar ectopy, and bacterial vaginosis or trichomonas vaginitis history were more risk factors for HPV infection. Factors for cervical lesion were similar, but in comparison with HPV infection, all associations were weakened. Only middle-aged women, husband's sexual partners, oral contraceptives, columnar ectopy, and history of trichomonas vaginitis remained associated with cervical lesion. CONCLUSION: In Beijing, the prevalence of cervical lesion and high-risk HPV is higher than estimated in previous reports. HPV 16, 58, and 33 were the most prevalent types. This is relevant for work related to cervical cancer vaccination. IMPACT: The study was conducted to understand the current status and epidemiologic characteristics of women with cervical lesion and HPV infection in Beijing.