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MicroRNAs (miRNAs) are a group of small, non-coding, and endogenous RNAs that regulate gene expression and over 50% of them are located at cancer-related genomic regions or fragile sites. According to previous studies there is significant association of miRNA single nucleotide polymorphisms (SNPs) with tumorigenesis (e.g., esophageal cancer, hepatocellular cancer, gastric cancer, bladder cancer, breast cancer, lung cancer, and colon cancer), however, the conclusions have been inconsistent. To investigate the relationship between miR-146a rs2910164 C G, miR-196a2 rs11614913 T C, and miR-499 rs3746444 A G polymorphisms and the susceptibility to esophageal squamous cell cancer (ESCC) in the Chinese Han nationality, we recruited 829 cases and 1522 controls in our study. In this case-control study, our results suggest that the rs3746444 GG genotype increased ESCC risk [homozygote model: adjusted odds ratio (OR), 2.26; 95% CI, 1.33-3.83; p = 0.003, recessive model: adjusted OR, 2.34; 95% CI, 1.38-3.96; p = 0.002], which remained consistent after Bonferroni correction. There was no association of rs11614913 and rs2910164 polymorphisms with ESCC. After adjusting by age, sex, smoking, and drinking status and body mass index (BMI), the multiple logistic analysis suggested that rs11614913 T → C variation reduced ESCC susceptibility in females and in the ≥63 years old subgroups, while rs2910164 C → G variation increased ESCC risk in both two BMI subgroups.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of unknown etiology affecting the colon and rectum. Previous studies have found that reactive oxygen species (ROS) overproduction and transmembrane glycoprotein CD98 (encoded by

The dietary inflammatory index (DII) is a scoring system to quantify the inflammatory effects of nutrients and foods. Inflammation may affect bone health. The purpose of this study was to explore the relationships of DII with bone mineral density (BMD) and osteoporosis.This study involved 1023 women and 1080 men (age ≥ 50) in the US National Health and Nutrition Survey (NHANES), 2017-2018. Multivariable linear regression models were used to estimate the associations between DII and BMD. Association between DII and osteoporosis was tested with multivariable logistic regression models.In women, DII was negatively associated with total hip and femoral neck BMD after adjusting for covariates (P lt; 0.05). In men, DII was negatively associated with lumbar spine BMD (P lt; 0.05). DII was positively associated with osteoporosis in women (P lt; 0.05). The odds ratios (ORs) (95% CI) for osteoporosis associated with DII quartiles 2, 3 and 4 vs. quartile 1 were 2.95 (1.08, 8.09), 5.63 (2.87, 11.04), and 6.14(2.55, 14.78), respectively. No significant association was observed in men.Higher DII scores were associated with increase osteoporosis risk in women, while no association was found in men. Greater pro-inflammatory diets might be associated with lower BMD in both women and men.

OBJECTIVE To investigate serum adiponectin and visfatin levels, and their ratio, in patients with endometrial cancer. METHODS A retrospective case-control study of 53 patients with endometrial cancer admitted to Dalian Municipal Women and Children's Medical Center, China, between May 1, 2009, and January 31, 2013. Ninety-eight healthy women who underwent physical examination at the same time served as the control group. Serum adiponectin and visfatin levels were measured by ELISA. RESULTS Serum adiponectin level in the endometrial cancer group was significantly lower than in the control group (2.09 ± 1.24 μg/mL vs 7.59 ± 2.29 μg/mL; P

Depression is one of the leading causes of disability burden and frequently co-occurs with multiple chronic diseases, but limited research has yet evaluated the correlation between multimorbidity and depression status by sex and age.29303 adults from 2005-2016 National Health and Nutrition Examination Survey were involved in the study. The validated Patient Health Questionnaire (PHQ-9) was used to assess depression status. The linear trend of the prevalence of multimorbidity was tested by logistic regressions, which was visualized by the weighted network. Gamma coefficient (γ) was used to evaluate the correlation between multimorbidity and depression status.The prevalence of multimorbidity in participants with no depression, mild depression, moderate depression and severe depression was 52.1%, 63.0%, 68.4% and 76.1%, respectively (p for trend0.001). In network analysis, the absolute network density increased with the levels of depression status (from 4.54 to 15.04). Positive correlation was identified between multimorbidity and depression status (γ=0.21, p0.001), and the correlation was different by sex and age, where it was stronger in women than men (females: γ=0.23, males: γ=0.16), and stronger in the young and the middle-age (young: γ=0.30, middle-age: γ=0.29, old: γ=0.22).This is a cross-sectional study and thus we cannot draw firm conclusions on causal correlations.Positive correlation between multimorbidity and depression status was identified, where the number of multimorbidity increased with the levels of depression status, especially in females, the young and the middle-age.

Background Observational studies have examined the association between fatty acid intake and breast cancer (BC), and the association might vary depending on menopausal status, but the results remain controversial. The objective of this study was to investigate the associations between fatty acid intake and BC. Methods The National Health and Nutrition Examination Survey (NHANES) 1999–2016 was used in the study, and stratified analysis by menopausal status was performed. Logistic regression models were used to evaluate the associations between BC and intake of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs), adjusting for covariates. Three two-sample Mendelian randomization (MR) methods—inverse variance weighted (IVW), weighted median, and Mendelian randomization–Egger (MR-Egger) regression—were applied to further verify the associations between intake of fatty acids and BC. Results Higher intake of MUFAs was associated with lower risk of BC in premenopausal women: ORs (95 %CI): 0.325 (0.110, 0.964). IVW showed that increased intake of MUFAs was associated with a reduced risk of BC: 0.997 (0.995, 1.000), p = 0.024. No associations between BC and SFAs, MUFAs or PUFAs were found in postmenopausal women or in the overall population. Conclusions Increasing intake of MUFAs might reduce the risk of BC in premenopausal women. The protective effect of MUFAs on BC was also supported by MR study.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease common in premature infants and is one of the leading causes of disability and death in newborns. The Keap-1/Nrf2 signaling pathway plays an important role in antioxidant and anti-inflammatory. Ten clean-grade, healthy pregnant Sprague-Dawley rats (purchased from Experimental Animal Center of Peking university, China) naturally gave birth to 55 neonatal rats from which 40 were selected and randomly divided into a hyperoxia group and a control group (N = 20, each). Thirty-two BPD patient samples are from Neonatal Department of the second Hospital of Jilin University from November 30, 2016 to May 1, 2019. In present study, we observed that lung tissues of the control group did not undergo obvious pathological changes, whereas in the hyperoxia group, lung tissues had disordered structures. With increased time of hyperoxia exposure, the alveolar wall became attenuated. Under hypoxia conditions, the activity of oxidative stress-related enzymes (CAT, GSH-Px, SOD) in lung samples was significantly lower than that before treatment. The expression level of Keap1 mRNA and protein in the hyperoxia group was slightly lower than that of control group. The expression of Nrf2 and HO-1 mRNA and protein in the hyperoxia group was significantly higher than that of control group. For the infants with BPD, we found that the activity of SOD, GSH-Px, and CAT was significantly different from those of control group. We constructed a premature BPD animal model and found the abnormal of oxidative stress in different groups and the expression levels of Keap1/Nrf2 signaling pathway-related molecules, and we validated the results in premature infants with BPD.

Breast cancer is the most common malignant tumor in women and one of the three most common cancers worldwide. It is a life-threatening disease among women and the leading cause of death among women. New drugs or new drug translations and laboratory clinical studies are ongoing. A new antitumor protein (PNAP) purified from edible fungus Pholiota nameko has potential for treating breast cancer. We have previously found that PNAP exhibits anti-proliferative and apoptosis-inducing activities in a human breast cancer cell line (MCF-7). In this study, we constructed a BALB/c mouse model of MCF-7 tumor xenografts. In vivo experiments show that PNAP can effectively inhibit the malignant proliferation of MCF-7 solid tumors. This is because PNAP can successfully activate the death receptor pathway and mitochondrial apoptosis pathway of MCF-7 tumor cells in vivo, and induce tumor cells to wither. It is estimated that PNAP may also have an immunoregulatory ability to indirectly inhibit malignant proliferation of tumors. We also found that PNAP may also have the immunomodulatory ability to indirectly inhibit the malignant proliferation of tumors, which can shift the balance of Th1/Th2 to Th1 and eventually inhibit the growth of tumors. The study reveals a new therapeutic approach for breast cancer patient.

Obstructive sleep apnea (OSA) is often associated with multisystem damage. The gut is a pivotal organ that initiates the pathophysiological processes of multisystem diseases. Intermittent hypoxia resulting from OSA may impair the intestinal barrier prior to the induction of systemic inflammation. We hypothesize that the intestinal barrier markers D-lactic acid (D-LA) and intestinal fatty acid-binding protein (I-FABP) levels would be higher in patients with OSA.Consecutive snoring and nonsnoring adults were included in this study and were grouped based on their apnea-hypopnea index (AHI) scores: the control group (AHI5) and the OSA group (AHI ≥ 5). Plasma D-LA and I-FABP levels were measured using colorimetry and ELISA, respectively. Other parameters, such as fasting levels of lipids, routine blood tests, and glucose were also assessed.Of 76 participants, patients in the OSA group accounted for 73% (55/76). Plasma D-LA and I-FABP levels were significantly higher in patients with OSA [7.90 (7.42) (IQR) vs. 0.88 (2.79) (IQR) mmol/L, p0.001 and 1851.99 ± 754.23 (SD) vs. 1131.98 ± 383.38 pg/mL, p0.001, respectively]. Increased glucose, triglycerides (TGs), leukocytes, neutrophils, and monocytes but decreased high density lipoprotein (HDL) were also found in patients with OSA. It was also observed that the increase in D-LA and I-FABP exhibited the strongest positive association with AHI (r = 0.443, p0.001; r = 0.645, p0.001), followed by the lowest SaO2 (p ≤ 0.001), BMI (p ≤ 0.017), glucose (p ≤ 0.011), and TGs (p ≤ 0.025). Moreover, multivariate regression analysis showed that D-LA (B = 0.823, p0.001) and I-FABP (B = 0.002, p = 0.017) were independently associated with OSA.The systemic expression of D-LA and I-FABP is dramatically higher in OSA patients, suggesting that hypoxia resulting from OSA might have the capacity to impair the intestinal barrier prior to the induction of multisystem dysfunction.

This study aims to prevent persistentinfection, reduce the incidence of cervical cancer, and improve women's health by understanding the theoretical basis of the risk factors for continuous infection of asymptomatic women with high-risk human papilloma virus (HPV) strains via information collected, which includes the persistent infection rate and the most prevalent HPV strain types of high risk to asymptomatic women in the high-risk area of cervical cancer in Linfen, Shanxi Province.Based on the method of cluster sampling, locations were chosen from the industrial county and agricultural county of Linfen, Shanxi Province, namely the Xiangfen and Quwo counties. Use of the convenience sampling (CS) method enables the identification of women who have sex but without symptoms of abnormal cervix for analyzing risk factors of HPV-DNA detection and performing a retrospective questionnaire survey in these 2 counties. Firstly, cervical exfoliated cell samples were collected for thin-layer liquid-based cytology test (TCT), and simultaneously testing high-risk type HPV DNA, then samples with positive testing results were retested to identify the infected HPV types. The 6-month period of testing was done to derive the 6-month persistent infection rate. The retrospective survey included concepts addressed in the questionnaire: basic situation of the research objects, menstrual history, marital status, pregnancy history, sexual habits and other aspects. The questionnaire was divided into a case group and a comparison group, which are based on the high-risk HPV-DNA testing result to ascertain whether or not there is persistent infection. Statistical analysis employed Epidate3.1 software for date entry, SPSS17.0 for date statistical analysis. Select statistic charts, Chi-Square Analysis, single-factor analysis and multivariate Logistic regression analysis to analyze the protective factors and risk factors of high-risk HPV infection. Risk factors are predicted by using the classification tree.3000 women participated in the study. The high-risk type HPV infection rate was 8.7%, the persistent infection rate was 7.5%. The persistent infection rates for the 2 age groups (ages 18-26 and 27-30) were 6.9% and 8.7%. The persistent infection rates of Xiangfen county were 7.4% and 7.4% respectively, and those of Quwo county were 7.8% and 11.6% respectively; there was no significant difference between each pair of groups. Single risk-factor analysis showed that first-time sex at age under 20, high school/technical secondary school education or above, multiple sexual partners, having more than 2 sexual partners in the past 6 months, oral sex, and colitis are the risk factors of high-risk type HPV infection. Multivariate analysis showed that the number of sexual partners, smoking and oral sex had an effect on HPV infection. The risk of HPV infection from smoking was 5.0-fold higher, and the risk of HPV infection from oral sex was 6.1-fold higher. Having more than 2 sexual partners increase the risk of HPV infection. By the predicated model analysis, the probability of HPV conveyed by oral sex was 14.8%; if the sexual companion number was zero or more than 2 without oral sex, the probability of HPV infection was 12.1%; if there was one sexual partner who smokes without oral sex, the probability of infection was 18.6%; if there was one sexual partner who does not smoke and without oral sex, the probability of infection was 3.6%.The persistent infection rate of asymptomatic women for high-risk type HPV is lower than those women in all ages. High-risk type HPV infection risk factors include the number of sexual partners, oral sex and smoking. Thus, young women may be able to reduce the risk of infection with high-risk type HPV by reducing the number of sexual partners, forming a correct sexual life habit, and avoiding smoking.

Background: Myocarditis is an inflammatory disease of the myocardium that may lead to cardiac death in some patients. However, little is known about the predictors of in-hospital mortality in patients with suspected myocarditis. Thus, the aim of this study was to identify the independent risk factors for in-hospital mortality in patients with suspected myocarditis by establishing a risk prediction model. Methods: A retrospective study was performed to analyze the clinical medical records of 403 consecutive patients with suspected myocarditis who were admitted to Ningbo First Hospital between January 2003 and December 2013. A total of 238 males (59%) and 165 females (41%) were enrolled in this study. We divided the above patients into two subgroups (survival and nonsurvival), according to their clinical in-hospital outcomes. To maximize the effectiveness of the prediction model, we first identified the potential risk factors for in-hospital mortality among patients with suspected myocarditis, based on data pertaining to previously established risk factors and basic patient characteristics. We subsequently established a regression model for predicting in-hospital mortality using univariate and multivariate logistic regression analyses. Finally, we identified the independent risk factors for in-hospital mortality using our risk prediction model. Results: The following prediction model for in-hospital mortality in patients with suspected myocarditis, including creatinine clearance rate (Ccr), age, ventricular tachycardia (VT), New York Heart Association (NYHA) classification, gender and cardiac troponin T (cTnT), was established in the study: P = ea/(1 + ea) (where e is the exponential function, P is the probability of in-hospital death, and a= −7.34 + 2.99 × [Ccr

Bisphenol AF (4,4'-hexafluoroisopropylidene-2-diphenol, BPAF), an endocrine disruptor, has been shown to stimulate the proliferation of human breast cancer cells. However, the underlying mechanism has not been fully elucidated. We found that BPAF promoted the in vitro proliferation of estrogen receptor α (ERα)-positive breast cancer cells (T47D and MCF7), but not ERα-negative cells (MDA-MB-231 and MDA-MB-435s). BPAF significantly stimulated the proliferation of cultured T47D cell in a dose-dependent manner, and the half-maximal effective concentration (EC50) was approximately 123 nM. We employed lentivirus-mediated short hairpin RNA (shRNA) to knockdown ERα and ER antagonist ICI 182780 to inhibit ER activation, which resulted in the repression of BPAF-induced proliferation of T47D and MCF7 cells. We observed that C-X-C chemokine ligand 12 (CXCL12) was up-regulated in T47D cells under treatment with BPAF. Quantitative real-time PCR results showed that BPAF caused a time and dose dependent increase in mRNA level of CXCL12. Furthermore, treatment of T47D cells with BPAF increased CXCL12 secretion according to ELISA assay. BPAF-induced CXCL12 transcription and secretion was significantly attenuated by small interfering RNA (siRNA) targeting ERα and ICI 182780, indicating BPAF-induced CXCL12 expression is mediated through ERα. Notably, knockdown CXCL12 in T47D cells significantly attenuated BPAF-induced cell proliferation. We also observed that inhibition of CXCL12 binding to its receptors CXCR4 and CXCR7 by chalcone 4 blocked BPAF-induced cell growth. Our results indicated that CXCL12 facilitated BPAF-induced proliferation of T47D cells. Taken together, our data provided support that BPAF stimulated transcription and secretion of CXCL12 depending on ERα, and ERα/CXCL12 signaling positively regulated BPAF-induced proliferation of cultured T47D breast cancer cells.

Patients with high on-treatment platelet reactivity (HPR) against aspirin or clopidogrel are at increased risk for adverse cardiovascular events. In this study, we explored the predictive value of common SNPs for the on-treatment platelet reactivity (OPR) against aspirin and clopidogrel assessed by VerifyNow assays.This study recruited 286 Han Chinese individuals undergoing antiplatelet treatment, including 159 cases with aspirin only (100 mg/day) and 127 cases with dual therapy (aspirin 100 mg/day plus clopidogrel 75 mg/day) for at least 2 weeks. The OPR against aspirin and clopidogrel were assessed by VerifyNow Aspirin (ARU) and P2Y12 assays (PRU), respectively. Genotyping for the selected 25 SNPs within 11 genes and 2 GWAS loci was carried out by ABI multiplex SNaPshot method.The results indicated that rs4244285 (CYP2C19) and rs342293 (7q22.3) were significantly associated with PRU value (both P 0.01). As for the OPR to aspirin, a weak statistical significance was observed in rs5445 (GNB3) (P = 0.049) and rs5758 (TBXA2R) (P = 0.045). After adjusting for the covariates including gender, age and smoking, carriers of allele A of rs4244285 remained as a strong predictor for HPR against clopidogrel.The current study suggests that common SNPs may predict OPR against clopidogrel as assessed by VerifyNow P2Y12, but are less likely to respond against aspirin as assessed by VerifyNow Aspirin.

Bisphenol AF (BPAF)-induced transcriptional activity has been evaluated by luciferase reporter assay. However, the molecular mechanism of BPAF-induced endogenous transcription in human breast cancer cells has not been fully elucidated. In the present study, we investigated the effect and mechanism of BPAF-induced endogenous transcription detected by real-time PCR in human breast cancer cells. We found that BPAF stimulated transcription of estrogen responsive genes, such as trefoil factor 1 (TFF1), growth regulation by estrogen in breast cancer 1 (GREB1) and cathepsin D (CTSD), through dose-dependent and time-dependent manners in T47D and MCF7 cells. Gene-silencing of ERα, ERβ and G protein-coupled estrogen receptor 1 (GPER) by small interfering RNA revealed that BPAF-induced endogenous transcription was dependent on ERα and GPER, implying both genomic and nongenomic pathways might be involved in the endogenous transcription induced by BPAF. ERα-mediated gene transcription was further confirmed by inhibition of ER activity using ICI 182780 in ERα-positive T47D and MCF7 cells as well as overexpression of ERα in ERα-negative MDA-MB-231 breast cancer cells. Moreover, we utilized Src tyrosine kinase inhibitor PP2 and two MEK inhibitors PD98059 and U0126 to elucidate the rapid nongenomic activation of Src/MEK/ERK1/2 cascade on endogenous transcription. Our data showed that BPAF-induced transcription could be significantly blocked by PP2, PD98059 and U0126, suggesting activation of ERK1/2 was also required to regulate endogenous transcription. Taken together, these results indicate that BPAF-induced endogenous transcription of estrogen responsive genes is mediated through both genomic and nongenomic pathways involving the ERα and ERK1/2 activation in human breast cancer cells.