The Role of von Willebrand Factor Antigen in Predicting Survival of Patients with HBV-Related Cirrhosis.

Objective: The model for end-stage liver disease (MELD) scoring system cannot be used to assess the deterioration of patients with liver cirrhosis caused by infection and portal hypertension. Elevated von Willebrand factor antigen (vWF-Ag) in plasma is associated with portal pressure and complications in patients with liver cirrhosis. We aimed to evaluate whether the addition of vWF-Ag can improve the risk prediction ability of the MELD scoring system. Methods: A total of 228 patients with hepatitis B virus (HBV)-related liver cirrhosis were eligible for inclusion in this retrospective study. The vWF-Ag level was assessed by enzyme-linked immunosorbent assay (ELISA). The endpoint of this study was defined as the time to liver transplantation or death. Univariate and multivariate analyses were performed to assess the risk factors associated with transplant-free mortality. Receiver operating characteristic (ROC) curve analysis was used to assess potential discriminatory variables for transplant-free mortality. Results: During a median follow-up interval of 30.23 months, 124 patients (54.4%) reached the endpoint of this study. Patients who died or underwent liver transplantation had elevated levels of MELD and vWF-Ag. Moreover, vWF-Ag and MELD showed comparable predictive potential for transplant-free survival (area under the curve [AUC], vWF-Ag = 0.71; AUC, MELD = 0.73). Ultimately, vWF-Ag can significantly improve the predictive potential of MELD in determining transplant-free mortality (AUC, MELD-vWF-Ag = 0.79, P = 0.006). Conclusion: An elevated vWF-Ag level was independently associated with transplant-free mortality in patients with liver cirrhosis. The inclusion of vWF-Ag in the MELD scoring system can improve mortality predictions in patients with liver cirrhosis.

Association between transforming growth factor-beta 1 polymorphisms and risk of pre-eclampsia: a meta-analysis.

PURPOSE: Pre-eclampsia (PE) is a common pregnancy-specific disorder characterized by hypertension and proteinuria. Previous studies have generated conflicting results regarding the association of transforming growth factor-beta 1 (TGF-ß1) gene polymorphisms (+869 T/C, -509 C/T, +915 G/C, and -800 G/A) with PE risk. Therefore, we conducted this meta-analysis to more precisely assess the role of TGF-ß1 gene polymorphisms in PE. METHODS: Eligible studies were retrieved from PubMed, Embase, Web of Science, Elsevier Science Direct, and several Chinese databases. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to calculate the associations. RESULTS: A total of 11 eligible studies (1463 cases/1754 controls) were included in this meta-analysis. A statistically significant association was found between the TGF-ß1 + 869 T/C polymorphism and PE risk in the Asian population and in subgroup analyses of the Hardy-Weinberg equilibrium (HWE) in controls and healthy pregnant controls. There was a statistically significant association between TGF-ß1 - 509 C/T polymorphism and PE risk among Asian women, and in the subgroup analysis of healthy pregnant controls. No obvious association was observed under any genetic model for the TGF-ß1 + 915 G/C and -800 G/A polymorphisms and PE risk, or between the TGF-ß1 + 869 T/C and -509 C/T polymorphisms and severity of PE. CONCLUSIONS: The present study suggested that the TGF-ß1 + 869 T/C and -509 C/T polymorphisms are associated with an increased risk of PE in the Asian population. Further case-controlled studies with larger sample sizes are needed to confirm our results.

Association of Plasma Fibrinogen Levels on Postoperative Day 1 with 2-Year Survival of Orthotopic Liver Transplantation for HBV-Related HCC.

OBJECTIVE: To clarify the prognostic values of hemostatic parameters to predict the survival of patients undergoing orthotopic liver transplantation (OLT) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: The data of 182 consecutive adult patients who underwent OLT for HBV-related HCC were subjected to univariate and multivariate analyses. RESULTS: Ascites and fibrinogen levels on postoperative day (POD) 1 were independent predictors of postoperative 2-year mortality (both P <.05). Kaplan-Meier survival analysis showed that the higher the fibrinogen level on POD 1, the better the 1- and 2-year survival of patients with ascites (P <.05), whereas the fibrinogen level on POD 1 was associated with 1-year (P <.05) but not 2-year survival of patients without ascites. CONCLUSION: Fibrinogen on POD 1 is a predictor of 2-year post-OLT survival of patients with HBV-related HCC with ascites.

Contribution of Lactobacillus iners to Vaginal Health and Diseases: A Systematic Review.

Lactobacillus iners, first described in 1999, is a prevalent bacterial species of the vaginal microbiome. As L. iners does not easily grow on de Man-Rogosa-Sharpe agar, but can grow anaerobically on blood agar, it has been initially overlooked by traditional culture methods. It was not until the wide application of molecular biology techniques that the function of L. iners in the vaginal microbiome was carefully explored. L. iners has the smallest genome among known Lactobacilli and it has many probiotic characteristics, but is partly different from other major vaginal Lactobacillus species, such as L. crispatus, in contributing to the maintenance of a healthy vaginal microbiome. It is not only commonly present in the healthy vagina but quite often recovered in high numbers in bacterial vaginosis (BV). Increasing evidence suggests that L. iners is a transitional species that colonizes after the vaginal environment is disturbed and offers overall less protection against vaginal dysbiosis and, subsequently, leads to BV, sexually transmitted infections, and adverse pregnancy outcomes. Accordingly, under certain conditions, L. iners is a genuine vaginal symbiont, but it also seems to be an opportunistic pathogen. Further studies are necessary to identify the exact role of this intriguing species in vaginal health and diseases.

Plasma Level of ADAMTS13 or IL-12 as an Indicator of HBeAg Seroconversion in Chronic Hepatitis B Patients Undergoing m-ETV Treatment.

The ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin motif repeats 13) is a key factor involved in coagulation process and plays a vital role in the progression and prognosis of chronic hepatitis B (CHB) patients with antiviral treatment. However, there are few reports about the profile of plasma ADAMTS13 in CHB patients during entecavir maleate (m-ETV) treatment. One hundred two HBV e antigen (HBeAg)-positive CHB patients on continuous m-ETV naive for at least 96 weeks were recruited. Patients with liver cirrhosis were excluded using liver biopsies and real-time elastography. Plasma ADAMTS13 and interleukin 12 (IL-12) levels were evaluated at baseline and12, 24, 48, 72, and 96 weeks, respectively. The change of ADAMTS13 (ΔADAMTS13) and IL-12 (ΔIL-12) possesses a significant relationship in CHB patients with HBeAg seroconversion (SC) at 48-week m-ETV treatment (p < 0.001), but no significance in patients without SC. Furthermore, Cox multivariate analysis demonstrated that the change of ADAMTS13 (IL-12) is an independent predictor for HBeAg SC at week 96, and the area under the receiver operating characteristic curve for the ΔADAMTS13 (ΔIL-12) in CHB patients with 48-week m- ETV treatment is 0.8204 (0.8354) (p < 0.001, both) to predict HBeAg SC at week 96. The results suggested that higher increased ADAMTS13 and IL-12 after 48-week m-ETV treatment contributed to an enhanced probability of HBeAg SC, although the mechanism is undetermined. Quantification of ADAMTS13 (IL-12) during m-ETV treatment may help to predict long-term HBeAg SC in CHB patients.

Lactobacillus iners Is Associated with Vaginal Dysbiosis in Healthy Pregnant Women: A Preliminary Study.

Vaginal dysbiosis has been identified to be associated with adverse pregnancy outcomes, such as preterm delivery and premature rupture of membranes. However, the overall structure and composition of vaginal microbiota in different trimesters of the pregnant women has not been fully elucidated. In this study, the physiological changes of the vaginal microbiota in healthy pregnant women were investigated. A total of 83 healthy pregnant participants were enrolled, who are in the first, second, or third pregnancy trimester. Quantitative real-time PCR was used to explore the abundant bacteria in the vaginal microbiota. No significant difference in the abundance of Gardnerella, Atopobium, Megasphaera, Eggerthella, Leptotrichia/Sneathia, or Prevotella was found among different trimesters, except Lactobacillus. Compared with the first pregnancy trimester, the abundance of L. iners decreased in the second and third trimester while the abundance of L. crispatus was increased in the second trimester. Moreover, we also found that vaginal cleanliness is correlated with the present of Lactobacillus, Atopobium, and Prevotella and leukocyte esterase is associated with Lactobacillus, Atopobium, Gardnerella, Eggerthella, Leptotrichia/Sneathia, and Prevotella. For those whose vaginal cleanliness raised or leukocyte esterase became positive, the richness of L. iners increased, while that of L. crispatus decreased significantly. Our present data indicated that the altered vaginal microbiota, mainly Lactobacillus, could be observed among different trimesters of pregnancy and L. iners could be considered as a potential bacterial marker for evaluating vaginal cleanliness and leukocyte esterase.

Increasing plasma ADAMTS13 activity is associated with HBeAg seroconversion in chronic hepatitis B patients during 5 years of entecavir treatment.

The relationship between hemostatic system and HBeAg seroconversion (SC) of chronic hepatitis B (CHB) patients is ill-defined. We therefore evaluate the predictive value of plasma ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin motif repeats 13) and VWF (von Willebrand factor) for CHB patients during 5-year entecavir (ETV) treatment. One hundred and fourteen HBeAg positive CHB patients on continuous ETV treatment were recruited. Liver biopsies were evaluated using the METAVIR scoring system, and plasma ADAMTS13 activity (ADAMTS13: AC) and VWF antigen (VWF: Ag) were determined at baseline, 3, 12, 24, 36, and 60 months, respectively. ETV treatment resulted in an increased ADAMTS13: AC and decreased VWF: Ag (both P < 0.001) in CHB patients. Cox multivariate analysis demonstrated that the change of ADAMTS13: AC after 1-year ETV treatment was an independent predictor for HBeAg SC at year 5. The area under the receiver operating characteristic (ROC) curve for the change of ADAMTS13: AC after 1-year ETV treatment plus baseline HBV DNA was 0.873 (P < 0.001) to predict SC at year 5. The results suggested that increased ADAMTS13: AC after 1 year ETV treatment was associated with a higher seroconversion, and could be used surrogate of HBeAg SC in CHB patients during 5-year ETV treatment.

D-dimer level in liver transplant recipients on the first day after surgery is correlated with postoperative thrombosis recurrence.

OBJECTIVE: This study aimed to investigate the relationship between plasma D-dimer level, preoperative complications, and thrombosis in liver transplant recipients. METHODS: The clinical data of 525 liver transplant recipients with end-stage liver disease (ESLD) in the First Affiliated Hospital of Zhejiang University from October 2012 to December 2015 were retrospectively analyzed. The patients were grouped based on thrombosis before and after surgery to determine the risk factors for postoperative thrombosis recurrence. RESULTS: Of the preoperative complications assessed, esophageal varices and thrombosis were significantly correlated (P = 0.000); ascites, spontaneous bacterial peritonitis, and hepatic encephalopathy were significantly correlated with preoperative D-dimer level (P < 0.001, P < 0.001, and P = 0.002, respectively); during the first week after surgery, the D-dimer level was significantly and consecutively higher than that before surgery and was significantly higher in the group with both preoperative and postoperative thrombosis than in the other groups on the first day after surgery (P < 0.001); the area under the curve (AUC) for diagnosis of postoperative thrombosis recurrence in the preoperative thrombosis group using plasma D-dimer level on the first day after surgery was 0.698 (P = 0.001); Cox regression analysis showed that D-dimer was an independent risk factor for postoperative thrombosis recurrence (HR = 3.062, P = 0.029). CONCLUSION: D-dimer level on the first day after liver transplant is related to thrombosis recurrence and is an independent risk factor for postoperative thrombosis recurrence.

Increased plasma prothrombin time is associated with poor prognosis in patients with paraquat poisoning.

BACKGROUND: Paraquat can cause severe injury to vascular endothelial cells and lead to coagulation dysfunction when it is taken into the blood by oral ingestion. In this study, we aim to find a routine coagulation index to serve as an indicator of outcome in patients with acute paraquat poisoning. METHODS: Between January 2012 and December 2016, 209 patients who attempted suicide by oral ingestion of paraquat were admitted to the emergency room. Routine coagulation indices, including plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fbg), thrombin time (TT), and D-dimer were measured to analyze the trend of changes and their relationship with prognosis. RESULTS: The results showed that the PT and APTT values in the ≥30 mL group were significantly greater than those in the <30 mL group (both P < .01). Within 1 week of admission, PT and APTT values gradually decreased, while Fbg levels gradually increased. Univariate and multivariate Cox regression analysis indicated that sex, ingestion volume, and PT were independent predictors of mortality within 40 days. The cumulative survival rates differed significantly (P = .001) between patients with PT <12 seconds and PT ≥12 seconds. CONCLUSIONS: Coagulation status in patients with PQ poisoning was closely related to prognosis. Routine monitoring of coagulation function, particularly PT in plasma, is helpful for analysis of the condition and prognosis of patients with PQ poisoning.

Increased von Willebrand factor over decreased ADAMTS-13 activity is associated with poor prognosis in patients with advanced non-small-cell lung cancer.

BACKGROUND: Hypercoagulability induced by the imbalance between von Willebrand factor (VWF) secretion and its cleaving protease (ADAMTS-13) has been correlated with cancer metastasis. The aim of this study was to explore the prognostic significance of the VWF/ADAMTS-13 ratio in advanced non-small-cell lung cancer (NSCLC). METHODS: Pre-treatment sera/plasma levels of VWF, ADAMTS-13, VWF/ADAMTS-13 ratio, factor (F) VIII, and other clinical/laboratory parameters were measured in 119 patients with advanced NSCLC and 102 healthy controls. All patients were followed up to determine the predictive value of these parameters for prognosis of advanced NSCLC. RESULTS: Elevated VWF, VWF/ADAMTS-13 ratio, and reduced ADAMTS-13 were significantly correlated with the stage and grade of advanced NSCLC and the final status of disease (P<.05). VWF levels and the VWF/ADAMTS-13 ratio were also associated with response to chemotherapy (P<.05). Multivariate analysis identified the VWF/ADAMTS-13 ratio and D-dimer as significant independent predictors of patient mortality. The area under the curve showed that the VWF/ADAMTS-13 ratio was more useful than VWF, ADAMTS-13, and D-dimer to predict mortality. Kaplan-Meier analysis showed that a low VWF/ADAMTS-13 ratio was significantly predictive of improved survival (P=.004). CONCLUSION: These results suggest that the imbalance between VWF secretion and ADAMTS-13 may play a critical role in the hypercoagulability state in advanced NSCLC. Moreover, elevation of the plasma VWF/ADAMTS-13 ratio may serve as an independent predictive factor for mortality in patients with advanced NSCLC.

Association of ABO blood groups with von Willebrand factor, factor VIII and ADAMTS-13 in patients with lung cancer.

Coagulative and fibrinolytic disorders appear to be associated with the development of lung cancer. The aim of the present study was to determine plasma levels of von Willebrand factor (VWF) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif 13 (ADAMTS-13), and factor VIII (FVIII) activity, in association with O and non-O blood groups in patients with lung cancer. Plasma levels of VWF and ADAMTS-13, and FVIII activity were measured in 115 patients with lung cancer and 98 healthy subjects. Phenotyping of the ABO blood groups was also performed for the two groups. Significantly increased VWF levels and FVIII activity, as well as significantly decreased ADAMTS-13 levels, were observed in patients with distant metastasis as compared with those without distant metastasis and the healthy controls. Plasma VWF levels and FVIII activity were significantly increased in subjects with non-O type blood compared with those with type O blood in the two groups. However, a significant decrease in ADAMTS-13 levels was observed only in the control group among those with non-O type blood, compared with those with type O blood. The results of the present study indicate that increased VWF and decreased ADAMTS-13 levels facilitate the invasiveness and metastasis of lung cancer. Non-O blood groups constitute a risk factor for increased VWF and FVIII in plasma. Continued monitoring of VWF and ADAMTS-13 levels, and of FVIII activity in patients with lung cancer with distinct blood groups may help to minimize the incidence of thrombotic events and improve assessment of disease progression.

Predictive value of serum ALT and T-cell receptor beta variable chain for HBeAg seroconversion in chronic hepatitis B patients during tenofovir treatment.

Effective antiviral therapy plays a key role in slowing the progression of chronic hepatitis B (CHB). Identification of serum indices, including hepatitis B e antigen (HBeAg) expression and seroconversion, will facilitate evaluation of the efficacy of antiviral therapy in HBeAg-positive CHB patients. The biochemical, serological, virological parameters, and the frequency of circulating CD4CD25 regulatory T cell (Treg) in 32 patients were measured at baseline and every 12 weeks during 96 weeks of tenofovir disoproxil fumarate (TDF) treatment. The relationship between the hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and Treg and alanine aminotransferase (ALT) levels was analyzed, respectively. The molecular profiles of T-cell receptor beta variable chain (TRBV) were determined using gene melting spectral pattern. For the seroconverted 12 patients, ALT declined to normal levels by week 24 and remained at this level in subsequent treatment; moreover, the predictive cutoff value of ALT for HBeAg seroconversion (SC) was 41.5 U/L at week 24. The positive correlation between HBV DNA and Treg and ALT was significant in SC patients, but not in non-SC patients. Six TRBV families (BV3, BV11, BV12, BV14, BV20, and BV24) were predominantly expressed in SC patients at baseline. The decline of ALT could be used to predict HBeAg seroconversion for CHB patients during TDF treatment. In addition, the profile of Tregs and TRBVs may be associated with HBeAg seroconversion and could also be a potential indicator for predicting HBeAg SC and treatment outcome for CHB patients.

Comparison of the prognostic values of inflammation markers in patients with acute pancreatitis: a retrospective cohort study.

OBJECTIVES: Inflammation-based prognostic markers (neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), red cell distribution width (RDW) and lymphocyte-monocyte ratio (LMR)) are associated with overall survival in some diseases. This study assessed their prognostic value in mortality and severity in acute pancreatitis (AP). DESIGN: A retrospective cohort study. SETTING: Patients with AP were recruited from the emergency department at our hospital. PARTICIPANTS: A total of 359 patients with AP (31 non-survivors) were enrolled. PRIMARY AND SECONDARY OUTCOME MEASURES: Mortality and severity of AP were the primary and secondary outcome measures, respectively. Biochemistry and haematology results of the first test after admission were collected. Independent relationships between severe AP (SAP) and markers were assessed using multivariate logistic regression models. Mortality prediction ability was evaluated using receiver operating characteristic (ROC) curves. Overall survival was evaluated using the Kaplan-Meier method, with differences compared using the log-rank test. Independent relationships between mortality and each predictor were estimated using the Cox proportional hazard models. RESULTS: Compared with survivors of AP, non-survivors had higher RDW (p<0.001), higher NLR (p<0.001), lower LMR (p<0.001) and lower PNI (p<0.001) at baseline. C reactive protein (CRP; OR=8.251, p<0.001), RDW (OR=2.533, p=0.003) and PNI (OR=7.753, p<0.001) were independently associated with the occurrence of SAP. For predicting mortality, NLR had the largest area under the ROC curve (0.804, p<0.001), with a 16.64 cut-off value, 82.4% sensitivity and 75.6% specificity. RDW was a reliable marker for excluding death owing to its lowest negative likelihood ratio (0.11). NLR (HR=4.726, p=0.004), CRP (HR=3.503, p=0.003), RDW (HR=3.139, p=0.013) and PNI (HR=2.641, p=0.011) were independently associated with mortality of AP. CONCLUSIONS: NLR was the most powerful marker of overall survival in this patient series.

Slow reduction of IP-10 Levels predicts HBeAg seroconversion in chronic hepatitis B patients with 5 years of entecavir treatment.

The aim of this study was to determine the correlation between dynamic changes in serum cytokine/chemokine expression levels in response to entecavir (ETV) treatment and HBV e antigen (HBeAg) seroconversion in patients with chronic hepatitis B (CHB). Four cytokines (interleukin [IL]-4, IL-6, IL-8, and interferon-γ) and five chemokines (macro-phage inflammatory protein [MIP]-1α, MIP-1ß, platelet derived growth factor-BB, and interferon-inducible protein 10 [IP-10]) before ETV therapy and at 3, 6, 12, 24, 36 and 60 months during therapy in 105 CHB patients were analyzed. The results showed that the low decrease rate of IP-10 levels after 1 year of ETV treatment was an independent predictor of HBeAg seroconversion at year 5 (Hazard ratio = 0.972). The area under the receiver operating characteristic curves for the decrease rate of IP-10 levels after 1 year of treatment to discriminate a year-5 HBeAg seroconversion was 0.752 (p = 0.005). The results indicate that higher IP-10 level at year one of ETV treatment is associated with an increased probability of HBeAg seroconversion. Quantification of IP-10 during ETV treatment may help to predict long-term HBeAg seroconversion in patients with CHB.

Molecular profile of the T cell receptor beta variable in peripheral blood lymphocytes from chronic asymptomatic HBV carriers.

T cell receptor beta variable (TCRBV) repertoire could imply the composition and function status of T cells in subjects with HBV infection. The gene melting spectral pattern (GMSP) can be used to determine the profile of TCRBV gene family. The molecular profile of TCRBV in peripheral lymphocytes from asymptomatic HBV carriers (AsC) remains ill-defined. Peripheral blood mononuclear cells (PBMCs) were separated and sorted, and the profiles of TCRBV complementarity-determining region 3 (CDR3) in CD4(+), CD8(+) T subsets and PBMCs were assayed using GMSP. The number of skewed TCRBV in the PBMCs was significantly lower than that in the CD4(+) or CD8(+) T subsets, and the number of monoclonal TCRBV families in the CD8(+) T subset was significantly higher than that in CD4(+) T subset. Compared to healthy donors, TCRBV11, BV13.1, BV20 and BV24 were used more frequently than other TCRBV members in PBMCs from AsC subjects. Furthermore, the relatively conserved CDR3 motifs were detected in these TCRBVs. The results indicate that the T cell response in AsC subjects involves several TCRBVs, and that the CD8(+) T subset maybe more relevant to pathogenesis of AsC. Moreover, the four relative conserved TCRBVs maybe a target for personalized treatments for persistent HBV infection.

Association of TNF-alpha, IL-6 and IL-1beta gene polymorphisms with polycystic ovary syndrome: a meta-analysis.

BACKGROUND: Several studies on the association of TNF-alpha (-308 G/A), IL-6 (-174 G/C) and IL-1beta (-511 C/T) polymorphisms with polycystic ovary syndrome (PCOS) risk have reported conflicting results. The aim of the present study was to assess these associations by meta-analysis. RESULTS: A total of 14 eligible articles (1665 cases/1687 controls) were included in this meta-analysis. The results suggested that there was no obvious association between the TNF-alpha (-308 G/A) polymorphism and PCOS in the overall population or subgroup analysis by ethnicity, Hardy-Weinberg equilibrium (HWE) in controls, genotyping method, PCOS diagnosis criteria, and study sample size. Also, no obvious association was found between the TNF-alpha (-308 G/A) polymorphism and obesity in patients with PCOS (body mass index [BMI] ≥ 25 kg/m(2) vs. BMI < 25 kg/m(2)). Regarding the IL-6 (-174 G/C) polymorphism, also no association was found in the overall population in heterozygote comparison, dominant model, and recessive model. Even though an allelic model (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.41-0.96) and a homozygote comparison (OR = 0.52, 95% CI = 0.30-0.93) showed that the IL-6 (-174 G/C) polymorphism was marginally associated with PCOS. Further subgroup analysis suggested that the effect size was not significant among HWE in controls (sample size ≤ 200) and genotyping method of pyrosequencing under all genetic models. Similarly, there was no association between the IL-1beta (-511 C/T) polymorphism and PCOS in the overall population or subgroup analysis under all genetic models. Furthermore, no significant association was found between the IL-1beta (-511 C/T) polymorphism and several clinical and biochemical parameters in patients with PCOS. CONCLUSIONS: The results of this meta-analysis suggest that the TNF-alpha (-308 G/A), IL-6 (-174 G/C), and IL-1beta (-511 C/T) polymorphisms may not be associated with PCOS risk. However, further case-control studies with larger sample sizes are needed to confirm our results.

Associations between estrogen receptor-beta polymorphisms and endometriosis risk: a meta-analysis.

BACKGROUND: Many epidemiological studies have suggested an association between estrogen receptor-beta (ER-ß) polymorphisms with endometriosis risk. However, the results of these studies have been inconsistent. In the present study, we performed a meta-analysis to clarify the associations between the ER-ß rs4986938 and rs1256049 polymorphisms and endometriosis risk. METHODS: Eligible publications were retrieved from the PubMed, ISI Web of Science, and several Chinese language databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random or fixed effect model. RESULTS: A total of eight studies (1100 cases/1485 controls) for the rs4986938 polymorphism and four studies (353 cases/450 controls) for the rs1256049 polymorphism were included in this meta-analysis. Regarding the rs4986938 polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis. In the subgroup analyses by ethnicity, study sample size, endometriosis-associated infertility, and stage of endometriosis, a significantly increased risk was observed among mixed populations (dominant model, OR=2.03, 95% CI=1.56-2.64) and among cases with endometriosis-associated infertility (dominant model, OR=1.83, 95% CI=1.26-2.67). Regarding the rs1256049 polymorphism, no obvious associations were found for all genetic models in the overall population. Subgroup analyses by ethnicity and study sample size revealed that only one study of a mixed population with small sample size showed an increased risk of endometriosis. No publication bias was found in the present study. CONCLUSIONS: The results of this meta-analysis suggest that the ER-ß rs4986938 and rs1256049 polymorphisms may not be associated with endometriosis risk, while the observed increased risk of endometriosis-associated infertility may be due to bias by the inclusion of small-scale studies. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_184.

Increased diversity of fungal flora in the vagina of patients with recurrent vaginal candidiasis and allergic rhinitis.

Recurrent vaginal candidiasis (RVC) is considered to be a hypersensitivity disorder that is associated with allergic rhinitis (AR) in immune deficiencies; however, whether or not the composition of the vaginal fungal flora in patients with AR and RVC is altered and if such alterations in patients with AR are associated with the development of RVC remain unclear. In the present study, a cultivation-independent method with the 18S rRNA gene clone library was used to analyze the diversity and composition of the vaginal fungal flora in patients with AR and RVC and to explore the association. Three fungal phyla (Ascomycotae, 22 out of 28; Basidiomycetes, 5 out of 28; and Oomycetes, 1 out of 28) were identified from groups of healthy volunteers, patients with AR, patients with RVC, and patients with RVC complicated by AR, including 28 phylotypes of fungal flora (10, 15, 17, and 21 phylotypes for each group, respectively). The predominant genera of fungi identified in the vagina included Candida, uncultured fungi, and Dothideomycetes. An increased proportion of Candida albicans accompanied with decreased proportions of Saccharomyces cerevisiae and uncultured fungi was observed in patients with AR or RVC (P < 0.05). Candida glabrata, Eladia saccula, Trichosporon jirovecii, and Phytophthora spp. occurred simultaneously in the three patient groups. The composition of the fungal communities in the four groups was statistically different (P < 0.001). The vaginal fungal diversity in patients with AR or RVC was significantly higher compared with healthy volunteers (P < 0.05). The data revealed an increased diversity and varied composition of the vaginal fungal flora in patients with AR and RVC and indicated that disturbed vaginal fungal flora in patients with AR might be correlated with disease progression in patients with RVC.

The transcription levels of ABCA1, ABCG1 and SR-BI are negatively associated with plasma CRP in Chinese populations with various risk factors for atherosclerosis.

ATP binding cassette transporters (ABCA1, ABCG1) and scavenger receptor class B type I (SR-BI) are the three most important cellular cholesterol transporters that may prevent atherogenesis. The aim of this study was to investigate whether they were altered in Chinese populations with various risk factors for atherosclerosis and their potential associations with C-reactive protein (CRP). Healthy female controls (n = 30) and populations with various risk factors for atherosclerosis, such as type 2 diabetes (n = 17), hypertension (n = 12), overweight/obesity (n = 10), incipient nephropathy (n = 10), postmenopausal women (n = 9), male (n = 19), ageing male (n = 22), or smoking (n = 16), were recruited. ABCA1, ABCG1 and SR-BI mRNA levels in peripheral monocytes was determined. ABCG1 was decreased in all the risk populations except ageing. ABCA1 was decreased in all the risk populations except diabetes and male. SR-BI was decreased in those with overweight/obesity and incipient nephropathy. Circulating CRP was increased almost in all the risk populations except in males. The levels of ABCA1, ABCG1 and SR-BI were reduced in those with subclinically high CRP, and negatively associated with CRP level. These data indicates that ABCA1, ABCG1, and SR-BI are reduced in various populations under subclinically inflammatory conditions, which may potentially lead to impairing reverse cholesterol transport and developing atherosclerosis.

Quantitative assessment of the associations between CYP1A1 polymorphisms and gastric cancer risk.

A great number of studies regarding the association between MspI and Ile462Val polymorphisms in the CYP1A1 gene and gastric cancer have been published. However, the results have been inconsistent. In this study, a meta-analysis was performed to investigate the associations. Published literature from PubMed, ISI Web of Science and other Chinese databases were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random or fixed effect model. Nine studies (860 cases/2183 controls) for CYP1A1 MspI polymorphism and nine studies (1161 cases/3273 controls) for CYP1A1 Ile462Val polymorphism were included in this meta-analysis. MspI polymorphism was not associated with gastric cancer risk (dominant model, OR = 0.95, 95%CI 0.80-1.14; recessive model, OR = 1.01, 95%CI 0.76-1.35; CC vs. TT, OR = 1.03, 95%CI 0.76-1.41; TC vs. TT, OR = 0.95, 95%CI 0.78-1.15). Similarly, there was no association between Ile462Val polymorphism and gastric cancer risk (dominant model, OR = 0.93, 95%CI 0.79-1.10; recessive model, OR = 1.34, 95%CI 0.90-2.00; GG vs. AA, OR = 1.27, 95%CI 0.84-1.90; AG vs. AA, OR = 0.87, 95%CI 0.71-1.07). In the subgroup analysis, no significant association was found in ever smokers, never smokers, Asians and Caucasians. This meta-analysis suggested that there were no associations between CYP1A1 polymorphisms and gastric cancer.