The prognostic value of tumor-infiltrating lymphocytes (TILs) in ovarian cancer is still in controversial. This study is aimed to assess the impact of different TIL subsets on the progression free survival (PFS)/disease free survival (DSS) and overall survival (OS)/disease specific survival (DSS) in ovarian cancer. A comprehensive literature search in PubMed, ISI Web of Science, and Medline was performed to identify relevant studies evaluating the prognostic value of TILs in ovarian cancer. Reviews of each study were conducted and data were extracted. The main outcomes analyzed were PFS/DFS and OS/DSS. A total of 21 eligible studies enrolling 2903 ovarian cancer patients were included for the meta-analysis. The overall analysis revealed that intraepithelial CD3+ and CD8+ TILs were strongly associated with improved PFS/DFS (HR=0.53, for CD3+ TILs; and HR=0.50, for CD8+ TILs). Intraepithelial CD8+/Foxp3+ ratios appeared to be associated with improved PFS, though without reaching statistical significance (HR=0.73). Moreover, intraepithelial CD3+, CD8+, and CD103+ TILs were clearly associated with increased OS/DSS (HR=0.50, for CD3+ TILs; HR=0.62, for CD8+ TILs; HR=0.54, for CD103+ TILs). However, intraepithelial FoxP3+ TILs, CD8+/FoxP3+ ratios, CD8+/CD4+ ratios, and stromal TILs had no impact on the OS/DSS (HR=0.98, for FoxP3+ TILs; HR=0.69, for CD8+/FoxP3+ ratios; HR=0.48, for CD8+/CD4+ ratios; HR=0.82, for stromal TILs). In conclusion, the present meta-analysis supports the hypothesis that intraepithelial TILs are predictive biomarkers for the prognosis of ovarian cancer patients. Future randomized studies are needed to verify these observations.

BackgroundNon-alcoholic fatty liver disease (NAFLD), recognized as the liver manifestation of metabolic syndrome, is highly prevalent in the general population. Recent studies suggest that lipid accumulation product is significantly associated with metabolic abnormalities. The aim of this study was to assess the accuracy of lipid accumulation product (LAP) as an effective screening tool for diagnosing NAFLD in the general population.MethodsA total of 40,459 subjects aged ≥18 years were enrolled in this cross-sectional study. LAP was calculated as [waist circumference (cm) – 65] × triglyceride concentration (mmol//L) in men and [waist circumference (cm) – 58] × triglyceride concentration (mmol/L) in women. Multiple logistic regression and receiver operating characteristic (ROC) analyses were performed.ResultsAccording to multiple logistic regression analyses, LAP was significantly associated with a higher prevalence and severity of NAFLD in both men and women. When assessed using ROC curve analyses, LAP exhibited high diagnostic accuracy for identifying NAFLD, and the areas under the curves (AUC) in men and women were 0.843 (95% CI 0.837, 0.849) and 0.887 (95% CI 0.882, 0.892), respectively. After further analyzed in different age groups, the diagnostic accuracy of LAP was found to be significantly better in younger age groups (aged 18-34 for men; aged 18-34 and 35-44 years for women) for both sexes.ConclusionsLAP is significantly associated with the presence and severity of NAFLD, and has a high diagnostic accuracy for identifying NAFLD in the general population. The diagnostic accuracy of LAP was especially high among younger age groups.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-017-0206-2) contains supplementary material, which is available to authorized users.

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BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and its prevalence is likely to rise even further. To help understand the pathogenesis and early prevention of progressive NAFLD, this large-scale study was designed to explore the potential association between homocysteine and the prevalence of NAFLD.MethodsA total of 7203 subjects aged 18 years or older were enrolled in this cross-sectional study. The association of homocysteine with the prevalence of NAFLD, in the total sample and stratified by subgroups, was examined using multiple logistic regression analyses.ResultsSubjects in the higher quartiles of homocysteine had a higher prevalence of NAFLD. After multivariate adjustment, the odds ratio (OR) for NAFLD in the highest compared with the lowest quartile of homocysteine was 2.08 (95% confidence interval [CI] 1.61, 2.67). Moreover, in the subgroup analyses, we found an effect modification by gender, body mass index (BMI) and smoking status on the association between homocysteine and the prevalence of NAFLD (P for interaction: 0.001, 0.002 and <0.001, respectively). A stronger association was observed in female, obese and non-smoking adults than in male, normal weight and smoking subjects.ConclusionHomocysteine was significantly associated with the prevalence of NAFLD, particularly in female, obese or non-smoking adults.

BackgroundThe clinical significance of hematogenous and lymphatic metastasis in ovarian cancer has been increasingly addressed, as it plays an imperative role in the formation of both intraperitoneal and distant metastases. Our objective is to identify the key molecules and biological processes potentially related to this relatively novel metastatic route in serous ovarian cancer.MethodsSince lymphovascular space invasion (LVSI) is considered as the first step of hematogenous and lymphatic dissemination, we developed a gene signature mainly based on the transcriptome profiles with available information on LVSI status in the Cancer Genome Atlas (TCGA) dataset. We then explored the underlying biological rationale and prognostic value of the identified gene signature using multiple public databases.ResultsWe observe that primary tumors with increased risk of hematogenous and lymphatic metastasis highly express a panel of genes, namely POSTN, LUM, THBS2, COL3A1, COL5A1, COL5A2, FAP1 and FBN1. The identified geneset is characterized by enhanced deposition of extracellular matrix and extensive stromal activation. Mechanistically, both the recruitment and the activation of stromal cells, especially fibroblasts, are closely associated with lymphovascular metastasis. Survival analysis further reveals that the elevated expression of the identified genes correlates to cancer progression and poor prognosis in patients with serous ovarian cancer.ConclusionsOur findings indicate that tumor stroma supports the hematogenous and lymphatic spread of ovarian cancer, increasing tumor invasiveness and ultimately resulting in worse survival. Thus stroma-targeted therapies may improve the clinical outcomes in combination with cytoreductive surgery and chemotherapy.

Objectives: To determine whether healthy lifestyle decreases the risk of developing hypertension in pre-hypertensive patients.Study design: A longitudinal study.Setting & participants: Randomly selected pre-hypertensive young adults 20-45 years old without any vascular disease such as stroke or diabetes.Predictors: Four lifestyle factors (a body mass index [BMI] of 18.5-24.9 kg/m2, regular physical activity, no alcohol use and 6-8 h of sleep per day), individually and in combination.Outcomes: Hypertension was defined as a systolic blood pressure (SBP) ≥ 140 mmHg, or a diastolic BP (DBP) ≥ 90 mmHg or self-reported hypertension.Measurements: Multivariate adjusted Cox proportional hazards.Results: During a median follow-up of 4.7 years, 1009 patients were enrolled in our study, and 182 patients developed hypertension. Compared with a BMI of 18.5-24.9 kg/m2, a BMI of 25-30 kg/m2 and a BMI of >30 kg/m2 were associated with an increased risk of hypertension occurrence (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.19-2.84 and HR, 2.62; 95% CI, 1.01-6.80, respectively). Compared with sleep duration of >8 h/day, 6-8 h/day of sleep was associated with a lower risk of hypertension occurrence (HR, 0.40; 95% CI, 0.18-0.86). There were no statistically significant associations between physical activity or alcohol use and hypertension occurrence (P>0.05).Limitation: All lifestyle factors were measured only once.Conclusion: Healthy BMI (18.5-24.9 kg/m2) and sleep duration (6-8 h/day) were associated with a lower risk of the occurrence of hypertension in pre-hypertension patients.

Introduction or backgroundPoorly-controlled hypertension in the first trimester significantly increases maternal and fetal morbidity and mortality. The majority of guidelines and clinical trials focus on the management and treatments for hypertension during pregnancy and breast-feeding, while limited evidence could be applied to the management for hypertension before pregnancy. In this review, we summarized the existing guidelines and treatments of pre-pregnancy treatment of hypertension.Sources of dataPubMed.Areas of agreementMethyldopa and labetalol are considered the first choice, but angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) need to be withdrawn if a hypertensive woman wishes to become pregnant. In women with chronic hypertension, it is very important to make an assessment before conception to exclude secondary causes of hypertension, evaluate their hypertensive control to ensure that it is optimal, discuss the increased risks of pre-eclampsia, and provide education regarding any drug alterations before they become pregnant.Areas of controversyThere is increasing debate regarding discouraging the use of diuretics. There is also controversy regarding the use of supplementations such as calcium, antioxidants and low-dose aspirin.Growing pointsA less restricted blood-pressure goal could be set for hypertensive women planning for pregnancy. A healthy body weight before pregnancy could lower the risk of pregnancy-related hypertensive disorders. Recent guidelines also encourage women with chronic hypertension to keep their dietary sodium intake low, either by reducing or substituting sodium salt before pregnancy.Timely areas for developing researchLarge, worldwide, randomized trials should be conducted to see the outcomes for hypertensive women who take antioxidants/physical activity before pregnancy.

Epithelial ovarian cancer is aggressive and lacks effective prognostic indicators or therapeutic targets. In the present study, using immunohistochemistry and bioinformatics analysis on ovarian cancer tissue data from The Obstetrics and Gynecology Hospital of Fudan University and The Cancer Genome Atlas database, it was identified that FXYD domain-containing ion transport regulator 5 (FXYD5) expression was upregulated in the SKOV3-IP cell line compared with its parental cell line, SKOV3, and in ovarian cancer tissues compared with in normal tissues. In addition, FXYD5 upregulation was predictive of poor patient survival. Furthermore, through various in vitro (Transwell assay, clonogenic assay and western blot analysis) and in vivo (nude mouse model) experiments, it was demonstrated that FXYD5 promoted the metastasis of ovarian cancer cells. Mechanistically, RNA sequencing, western blot analysis, a luciferase reporter assay and chromatin immunoprecipitation were performed to reveal that FXYD5 dispersed the SMAD7-SMAD specific E3 ubiquitin protein ligase 2-TGF-β receptor 1 (TβR1) complex, deubiquitinated and stabilized TβR1, and subsequently enhanced transforming growth factor-β (TGF-β) signaling and sustained TGF-β-driven epithelial-mesenchymal transition (EMT). The TGF-β-activated SMAD3/SMAD4 complex was in turn directly recruited to the FXYD5 promoter region, interacted with specific SMAD-binding elements, and then promoted FXYD5 transcription. In brief, FXYD5 positively regulated TGF-β/SMADs signaling activities, which in turn induced FXYD5 expression, creating a positive feedback loop to drive EMT in the process of ovarian cancer progression. Collectively, the findings of the present study suggested a mechanism through which FXYD5 serves a critical role in the constitutive activation of the TGF-β/SMADs signaling pathways in ovarian cancer, and provided a promising therapeutic target for human ovarian cancer.