Biomethanation of syngas at high CO concentration in a continuous mode.

Syngas from pyrolysis/gasification process is a mixture of CO, CO2 and H2, which could be converted to CH4, so called syngas biomethanation. Its development is obstructed due to the low productivity and CO inhibition. The aim of this study was to demonstrate the feasibility of using syngas as the only carbon source containing high CO concentration (40%) for biomethanation. Lab-scale thermophilic bioreactor inoculated with anaerobic sludge was operated continuously for over 900 h and the shift of microbial structure were investigated. Results showed that thermophilic condition was suitable for syngas biomethanation and the microbes could adapt to high CO concentration. Higher processing capacity of 12.6 m3/m3/d was found and volumetric methane yield of 2.97 m3/m3/d was observed. These findings could strengthen the theoretical basis of syngas biomethanation and support its industrialization in the future.

Particle Swarm Algorithm-Based Analysis of Pelvic Dynamic MRI Images in Female Stress Urinary Incontinence.

This work aimed to study the application of pelvic floor dynamic images of magnetic resonance imaging (MRI) based on the particle swarm optimization (PSO) algorithm in female stress urinary incontinence (SUI). 20 SUI female patients were selected as experimental group, and another 20 healthy females were taken as controls. PSO algorithm, K-nearest neighbor (KNN) algorithm, and back propagation neural network (BPNN) algorithm were adopted to construct the evaluation models for comparative analysis, which were then applied to 40 cases of female pelvic floor dynamic MRI images. It was found that the model proposed had relatively high prediction accuracy in both the training set (87.67%) and the test set (88.46%). In contrast to the control group, there were considerable differences in abnormal urethral displacement, urethral length changes, bladder prolapse, and uterine prolapse in experimental patients (P < 0.05). After surgery, the change of urethral inclination angle was evidently reduced (P < 0.05). To sum up, MRI images can be adopted to assess the occurrence of female SUI with abnormal urethral displacement, shortening of urethra length, bladder prolapse, and uterine prolapse. After surgery, the abnormal urethral movement was slightly improved, but there was no obvious impact on bladder prolapse and uterine prolapse.

Construction of a comprehensive nutritional index and comparison of its prognostic performance with the PNI and NRI for survival in older patients with nasopharyngeal carcinoma: a retrospective study.

OBJECTIVES: To explore the relationship between the Comprehensive Nutritional Index (CNI) and survival in older patients with nasopharyngeal carcinoma (NPC) and to compare the prognostic performance of three nutritional indicators (CNI, Prognostic Nutritional Index (PNI), and Nutritional Risk Index (NRI)) for overall survival (OS). METHODS: This retrospective study involved 309 older NPC patients in Guangzhou (China) from November 2006 to November 2017. The CNI comprised five parameters: the body mass index (BMI), usual body weight percentage (UBW%), hemoglobin (Hb) level, albumin level, and total lymphocyte count (TLC). All single nutritional indicators were evaluated before and immediately after treatment. The principal component analysis (PCA) was used for calculation of the CNI by single nutritional indicators after treatment. The cutoff point for the CNI was evaluated and logistic regression used to explore the risk factors for the CNI. Univariable, multivariable Cox regression, and Kaplan-Meier methods were applied for OS and disease-free survival (DFS) analyses. Cox proportional hazards models were used to compare the prognostic value of the CNI, PNI, and NRI for OS. RESULTS: All single nutritional indicators decreased significantly after treatment (P < 0.05). The CNI cutoff point for mortality was 0.027, and the logistic regression indicated more complex treatments or higher cancer stage for NPC was associated with a low CNI (HR = 0.179; 95% CI: 0.037-0.856; 0.545, 0.367-0.811, respectively). In multivariable Cox regression, the CNI remained an independent prognostic factor of OS and DFS (HR = 0.468, 95% CI: 0.263-0.832; 0.527, 0.284-0.977, respectively). Kaplan-Meier curves showed that a low CNI was associated with worse OS and DFS (P = 0.001 and 0.013, respectively). The prognostic predictive performance of the CNI was superior to that of the PNI or NRI. CONCLUSIONS: The CNI can be recommended as an appropriate indicator reflecting the integrated nutritional status of older NPC patients. A low CNI predicted a poor survival outcome and the prognostic performance of CNI was superior to PNI or NRI.

Nutrition counseling combined with head and neck rehabilitation exercises can enhance outcomes among nasopharyngeal carcinoma patients in southern China: a prospective study in an epidemic area.

BACKGROUND: More than two thirds of new of nasopharyngeal carcinoma (NPC) cases occurring in the east and southeast parts of Asia. As a consequence, the development of intervention programs that can educate and assist patients of NPC in adopting and maintaining long-term behavioral changes to prevent further progression of the disease and improve quality of life represents a continuing need. METHODS: Patients diagnosed with NPC (n=141) completed chronic disease self-management questionnaires (CDSMP) before, immediately after, and 3, 6, and 12 months after receiving primary cancer treatment. An independent-samples T test was used to compare mean changes in chronic disease self-management (CDSM) items between the intervention group and control group. RESULTS: There was no difference between the two groups at baseline. Patients who received an intervention demonstrated a significant improvement in fatigue and shortness of breath after treatment. They also demonstrated significant improvements in weekly minutes of aerobic exercise and stretching/strengthening exercise. These advantages lessened slightly with elapsed time. CONCLUSIONS: For NPC patients, nutrition counseling combined with head and neck rehabilitation exercises can greatly reduce fatigue and shortness of breath and greatly increase the use of stretching/strengthening and aerobic exercise 3 months after intensity-modulated radiotherapy (IMRT).

Bisphenol A exposure induces gut microbiota dysbiosis and consequent activation of gut-liver axis leading to hepatic steatosis in CD-1 mice.

Interactions between the intestine and the liver, the so-called 'gut-liver axis', play a crucial role in the onset of hepatic steatosis and non-alcoholic fatty liver disease. However, not much is known about the impact of environmental pollutants on the gut-liver axis and consequent hepatic steatosis. Bisphenol A (BPA), a widely used plasticiser, is an important environmental contaminant that affects gut microbiota. We hypothesised that BPA induces hepatic steatosis by promoting gut microbiota dysbiosis and activating the gut-liver axis. In this study, male CD-1 mice were fed with diet containing BPA (50 µg/kg body weight/day) for 24 weeks. Dietary exposure to BPA increased lipid contents and fat accumulation in the liver. Analysis of 16 S rRNA gene sequencing revealed that the diversity of gut microbiota reduced and the composition of gut microbiota was altered in the BPA-fed mice. Further, the abundance of Proteobacteria, a marker of dysbacteria, increased, whereas the abundance of Akkermansia, a gut microbe associated with increased gut barrier function and reduced inflammation, markedly decreased. Expression levels of intestinal tight junction proteins (zona occludens-1 and occludin) also decreased drastically, leading to increased intestinal permeability and elevated levels of endotoxins. Furthermore, BPA up-regulated the expression of Toll-like receptor 4 (TLR4) and phosphorylation of nuclear factor-kappa B (NF-κB) in the liver and increased the production of inflammatory cytokines, including interleukin-1ß, interleukin-18, tumour necrosis factor-α, and interleukin-6. Take together, our work indicated that dietary intake of BPA induced hepatic steatosis, and this was closely related to dysbiosis of gut microbiota, elevated endotoxin levels, and increased liver inflammation through the TLR4/NF-κB pathway.

Urolithin A attenuated ox-LDL-induced cholesterol accumulation in macrophages partly through regulating miR-33a and ERK/AMPK/SREBP1 signaling pathways.

Promoting cholesterol efflux from foam cells represents one of the therapeutic strategies for ameliorating atherosclerosis. Urolithin A (UA) has been shown before to attenuate ox-LDL induced endothelial dysfunction in endothelial cells with its anti-inflammatory properties. The aim of this study was to investigate whether UA could promote cholesterol efflux via modulating related microRNA (miR) and signaling pathways. RAW264.7 cells were treated with 50 µg mL-1 ox-LDL to induce foam cell formation. After treatment with UA at different concentrations, intercellular and extracellular cholesterol levels were determined. Expression of Erk1/2, AMPKα and their phosphorylation forms, and SREBP1, was analyzed by western-blotting. The effect of UA on miR-33a expression and the involvement of miR-33a in cholesterol efflux regulation were also investigated. UA reduced ox-LDL induced cholesterol accumulation in macrophage cells and promoted cholesterol efflux from cells. Compared with ox-LDL treated cells, UA treatment reduced the level of phosphorylated ERK1/2, increased the expression of phosphorylated AMPKα and decreased the SREBP1 expression. Moreover, UA decreased the miR-33a expression at the transcriptional level but increased the transcriptional expression of ATP-binding cassette transporter A1 (ABCA1) and ABCG1, two genes contributing to reverse cholesterol transport. Furthermore, pre-miR-33a attenuated cholesterol efflux induced by UA. Collectively, UA promoted the reverse cholesterol transport in macrophage-derived foam cells and interfered with cholesterol metabolism possibly through regulating the miRNA-33 expression and interaction with the ERK/AMPKα/SREBP1 signaling pathway.

Protocatechuic Acid Inhibits Vulnerable Atherosclerotic Lesion Progression in Older Apoe-/- Mice.

BACKGROUND: Normalization of arterial inflammation inhibits atherosclerosis. The preventive role for protocatechuic acid (PCA) in early-stage atherosclerosis is well recognized; however, its therapeutic role in late-stage atherosclerosis remains unexplored. OBJECTIVE: We investigated whether PCA inhibits vulnerable atherosclerosis progression by normalizing arterial inflammation. METHODS: Thirty-wk-old male apolipoprotein E-deficient (Apoe-/-) mice with vulnerable atherosclerotic lesions in the brachiocephalic artery were fed the AIN-93G diet alone (control) or supplemented with 0.003% PCA (wt:wt) for 20 wk. Lesion size and composition, IL-1ß, and NF-κB in the brachiocephalic arteries, and serum lipid profiles, oxidative status, and proinflammatory cytokines (e.g., IL-1ß, monocyte chemoattractant protein-1, and serum amyloid A) were measured. Moreover, the effect of PCA on the inflammation response was evaluated in efferocytic macrophages from C57BL/6J mice. RESULTS: Compared with the control treatment, dietary PCA supplementation significantly reduced lesion size (27.5%; P < 0.05) and also improved lesion stability (P < 0.05) as evidenced by increased thin fibrous cap thickness (31.7%) and collagen accumulation (58.3%), reduced necrotic core size (37.6%) and cellular apoptosis (73.9%), reduced macrophage accumulation (45.1%), and increased vascular smooth muscle cell accumulation (51.5%). Moreover, PCA supplementation inhibited IL-1ß expression (53.7%) and NF-κB activation (64.4%) in lesions. However, PCA supplementation did not change serum lipid profiles, total antioxidant capacity, and inflammatory cytokines. In efferocytic macrophages, PCA at 0.5 and 1 µmol/L inhibited Il1b/IL-1ß mRNA (27.2-46.5%) and protein (29.2-49.6%) expression and NF-κB activation (67.0-80.3%) by upregulation of MER proto-oncogene tyrosine kinase (MERTK) and inhibition of mitogen-activated protein kinase 3/1 (MAPK3/1). Strikingly, the similar pattern of the MERTK and MAPK3/1 changes in lesional macrophages of mice after PCA intervention in vivo was recapitulated. CONCLUSION: PCA inhibits vulnerable lesion progression in mice, which might partially be caused by normalization of arterial inflammation by upregulation of MERTK and inhibition of MAPK3/1 in lesional macrophages.

Effects of temperature, hydrogen/carbon monoxide ratio and trace element addition on methane production performance from syngas biomethanation.

Synthesis gas (Syngas) biomethanation is an environmentally friendly technology for fuel calorific value improvement. However, the slow mass transfer and poor product quality limit its development. In this study, the effects of temperature, hydrogen/carbon monoxide (H2/CO) ratio and trace element addition on simulated syngas biomethanation were investigated in three batches of experiments. Results showed that (1) the temperature influenced little on the quality of produced biogas; (2) the methane content in the biogas production were 66.37 ±â€¯4.04%, 70.61 ±â€¯6.06% and 73.35 ±â€¯2.39% respectively with the H2/CO ratio of 3:1, 4:1 and 5:1; (3) after the addition of Fe, Co and Ni elements, the biogas quality was significantly improved (methane content was 79.76 ±â€¯7.35%), but the microbial community structure did not change. This experiment provided a guidance for improving the biogas production performance of syngas biomethanation.

Citral Attenuated Intestinal Inflammation Induced by Cronobacter sakazakii in Newborn Mice.

Necrotizing enterocolitis (NEC) is a serious inflammatory intestinal disorder with a high mortality rate, which occurs most commonly in newborn infants. Cronobacter sakazakii, a common contaminant in infant formula, is associated with NEC. However, its role in NEC pathogenesis is unknown, and there are still no effective treatments for NEC. Currently, natural bioactive products have been investigated for their beneficial effects in preventing microbial infection. In this study, a neonatal mouse intestinal inflammation model was used to examine the protective effects of citral (a natural bioactive product) on C. sakazakii-induced intestinal inflammation and damages. It was shown that citral reduced the number of C. sakazakii cells in ileal tissues, and mice treated with citral had a significantly higher body weight than C. sakazakii-infected mice. Citral treatment also ameliorated serious ileal tissue damages, including epithelial sloughing, villous rupture, and enterocyte apoptosis. C. sakazakii infection upregulated the messenger RNA transcription levels of several inflammation-associated genes, increased production of IL-6 and TNF-α, and activated the NF-κB and MAPK signaling pathways in ileal tissues. Citral treatment mitigated these inflammatory responses. The apoptotic index and activities of caspase 3, 8, and 9 increased in murine ileum after C. sakazakii infection, but citral inhibited both enterocyte apoptosis and activations of these caspase. These findings suggest that citral has protective effects on C. sakazakii-induced intestinal inflammation in newborn mice, and it may play a future role in the management of C. sakazakii-associated infections and diseases.

Curcumin prevents high-fat diet-induced hepatic steatosis in ApoE-/- mice by improving intestinal barrier function and reducing endotoxin and liver TLR4/NF-κB inflammation.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and has become a public health concern worldwide. The hallmark of NAFLD is hepatic steatosis. Therefore, there is an urgent need to develop new therapeutic strategies that are efficacious and have minimal side effects in hepatic steatosis and NAFLD treatment. The present study aimed to investigate the effect of dietary supplement of curcumin on high-fat diet (HFD)-induced hepatic steatosis and the underlying mechanism. METHODS: ApoE-/- mice were fed a normal diet, high-fat diet (HFD) or HFD supplemented with curcumin (0.1% w/w) for 16 weeks. Body and liver weight, blood biochemical.parameters, and liver lipids were measured. Intestinal permeability, hepatic steatosis and mRNA and protein expressions of TLR4-related inflammatory signaling molecule were analyzed. RESULTS: The administration of curcumin significantly prevented HFD-induced body weight gain and reduced liver weight. Curcumin attenuated hepatic steatosis along with improved serum lipid profile. Moreover, curcumin up-regulated the expression of intestinal tight junction protein zonula occluden-1 and occludin, which further improved gut barrier dysfunction and reduced circulating lipopolysaccharide levels. Curcumin also markedly down-regulated the protein expression of hepatic TLR4 and myeloid differentiation factor 88 (MyD88), inhibited p65 nuclear translocation and DNA binding activity of nuclear factor-κB (NF-κB) in the liver. In addition, the mRNA expression of hepatic tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) as well as the plasma levels of TNF-α and IL-1ß were also lowered by curcumin treatment. CONCLUSION: These results indicated that curcumin protects against HFD-induced hepatic steatosis by improving intestinal barrier function and reducing endotoxin and liver TLR4/NF-κB inflammation. The ability of curcumin to inhibit hepatic steatosis portrayed its potential as effective dietry intervention for NAFLD prevention.

Lymphadenectomy is associated with poor survival in patients with gastrointestinal stromal tumors.

BACKGROUND: Current clinical practice suggests lymphadenectomy for gastrointestinal stromal tumor (GIST) patients with enlarged lymph nodes, but little is known about the influence of lymphadenectomy on long-term survival. METHODS: This population-based study consisted of 3,819 non-metastatic GIST patients diagnosed between January 1st, 2001, to December 31st, 2015, from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier methods and Cox proportion regression models were used to compare differences in overall survival (OS) and cancer-specific survival (CSS) between the lymphadenectomy group and non-lymphadenectomy group. RESULTS: Among the 3,819 GIST patients, 1,202 received lymphadenectomy and 2,617 did not receive lymphadenectomy. Lymphadenectomy was associated with poor OS (adjusted HR =1.25, 95% CI: 1.06-1.47) and CSS (adjusted HR =1.32, 95% CI: 1.07-1.64) in GIST patients. This was especially evident in GIST patients with a tumor size less than 2 cm (OS, HR =1.91, 95% CI: 0.79-4.60 and CSS, HR =6.37, 95% CI: 1.85-21.90), who were more than 40 years old (OS, HR =1.28, 95% CI: 1.08-1.51 and CSS, HR =1.36, 95% CI: 1.09-1.70), and with a stomach tumor (OS, HR =1.39, 95% CI: 1.12-1.72 and CSS, HR =1.77, 95% CI: 1.33-2.35). CONCLUSIONS: In conclusion, contrary to what was previously presumed, lymphadenectomy was associated with an increased and not a decreased risk of mortality in GIST patients.

Prognostic significance of perioperative chemotherapy on resectable colorectal mucinous adenocarcinoma liver metastasis.

BACKGROUND: Mucinous adenocarcinoma (MAC) is an uncommon subtype of colorectal cancer (CRC). For colorectal cancer liver metastasis (CRLM), perioperative chemotherapy (PCT) has been developed to improve the rate of resection and reduce the rate of early recurrence; however, its impact on long-term outcomes in MAC is unclear. METHODS: From 1999 to 2016, 442 patients with CRLM were retrospectively reviewed, all of whom underwent CRC resection and liver metastasis resection. Among them, 34 were MAC, and the others were non-MAC. A total of 102 non-MAC patients with CRLM who underwent surgery at the same period were matched with 34 MAC patients in a ratio of 3:1 by using a random number table for analysis. RESULTS: Clinicopathologic characteristics for the MAC group (n=34) and non-MAC group (n=102) had no statistical difference. Both recurrence free survival (RFS) and overall survival (OS) did not significantly differ between the two groups. Nevertheless, in the non-MAC group, OS was fundamentally prolonged in patients with PCT compared to those who didn't have PCT (P=0.031). CONCLUSIONS: In this study, PCT had a survival benefit on non-MAC patients with CRLM while MAC patients with resectable CRLM do not benefit from PCT. When developing treatment like PCT or surgery alone for CRLM, mucinous histology should be considered as an important influence factor.

Bisphenol A exposure induces cholesterol synthesis and hepatic steatosis in C57BL/6 mice by down-regulating the DNA methylation levels of SREBP-2.

Bisphenol A (BPA), a major plasticizers that are commonly used for lining of beverage or food-storage containers, has been shown to increase cholesterol levels with molecular mechanism not clear. The present study was aimed to investigate the effects of BPA exposure on liver cholesterol synthesis and hepatic steatosis in male C57BL/6 mice and its underlying mechanisms. Male C57BL/6 mice were exposed to different doses (50, 500 and 5000 µg/kg/day) of BPA through diet for 16 weeks. Exposure to low doses (50 and 500 µg/kg/day) of BPA increased hepatic cholesterol content and the expression levels of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and sterol regulatory element binding proteins-2 (SREBP-2). DNA methylation analysis further showed that mice exposed to low-dose BPA decreased the DNA methylation levels of SREBP-2. Moreover, low doses of BPA exposure increased the expression levels of SREBP-1c and stearoyl-CoA desaturase 1 in the liver, and induced hepatic lipid synthesis and fat accumulation. Our results suggest that low-dose BPA exposure could induce hepatic cholesterol synthesis through decreasing the DNA methylation levels of SREBP-2 and subsequently up-regulating the expression of genes related to cholesterol synthesis in the liver, which causes cholesterol accumulation and further induces liver lipid synthesis and hepatic steatosis.

Exploration of Racial Differences in Reproductive Factors for Breast Cancer among Women aged 55-74.

Background Reproductive factors have been well-documented risk factors for breast cancer. Few studies have examined whether the associations between reproductive factors and breast cancer differed across races/ethnicities. Methods We analyzed a sub-sample (70, 734) of the Prostate, Lung, Colorectal, and Ovarian (PLCO) dataset. Participants with valid baseline questionnaire and without breast cancer at enrollment were included into analysis. We stratified the participants into subgroups based on their races/ethnicities then estimated the effects of the reproductive factors on breast cancer within each group using Cox-proportion regression models. Results Oral contraceptive use (HR=1.09, 95% confidence interval or CI=1.01, 1.18), advanced age at natural menopause (HR=1.25, 95% CI=1.06, 1.49) were associated with increased risk of breast cancer in non-Hispanic Caucasians group only. Long term use of menopausal hormone therapy (more than five years) was associated with increased risk of breast cancer in both of the non-Hispanic Caucasian (HR=1.44, 95% CI=1.31, 1.59) group and the non-Hispanic Asian/Pacific Islander (HR=1.98, 95% CI=1.23, 3.20) group, but not in other race/ethnic groups. Hispanics who tried to become pregnant for a year or more had increased risk of breast cancer (HR=2.60, 95% CI=1.05, 6.46) than their counterparts without difficulty in getting pregnancy. In addition, surgery induced menopause was found to be a protective factor for breast cancer in non-Hispanic Caucasian (HR=0.88, 95% CI=0.79, 0.98) group only. Conclusions We concluded that different races/ethnicities had different breast cancer related reproductive risk factors. Non-Hispanic Caucasians had the most breast cancer related reproductive risk factors, while the minorities had none or few breast cancer related reproductive risk factors and among these few factors only 1 was also risk factor for non-Hispanic Caucasians.

Associations of plasma hepcidin with mortality risk in patients with coronary artery disease.

BACKGROUND: Increased blood hepcidin may be associated with the presence and promotion of atherosclerosis, the association of hepcidin with mortality among coronary artery disease (CAD) patients remains unknown. We sought to assess the relationship of hepcidin and all-cause and cardiovascular disease (CVD) mortality among CAD patients with and without acute coronary syndrome (ACS). METHODS AND RESULTS: This study included 759 patients with ACS and 526 patients with stable CAD. After an average follow-up of 4.1 years, 154 deaths were recorded, 114 were due to CVD. After adjusting for CVD risk factors and inflammatory markers, the plasma hepcidin was positively associated with all-cause and CVD mortality in the ACS patients, the multivariable-adjusted hazard ratios (HRs) across tertiles of hepcidin were 1.00, 2.18 (95% CI 1.23-3.94), and 2.82 (95% CI 1.59-5.12) for all-cause mortality (Ptrend=0.006), and 1.00, 2.20 (95% CI 1.12-4.05), and 2.64 (95% CI 1.41-5.65) for CVD mortality (Ptrend=0.01). The C-index and net reclassification improvement when including hepcidin in traditional CVD models were 1.6% and 21.5% for all-cause mortality, 1.4% and 23.5% for CVD mortality, respectively, (P<0.001). CONCLUSIONS: Plasma hepcidin was positively associated with mortality in ACS patients. Hepcidin may be a potential biomarker for risk prediction in ACS patients.

High-calorific biogas production from anaerobic digestion of food waste using a two-phase pressurized biofilm (TPPB) system.

To obtain high calorific biogas via anaerobic digestion without additional upgrading equipment, a two-phase pressurized biofilm system was built up, including a conventional continuously stirred tank reactor and a pressurized biofilm anaerobic reactor (PBAR). Four different pressure levels (0.3, 0.6, 1.0 and 1.7MPa) were applied to the PBAR in sequence, with the organic loading rate maintained at 3.1g-COD/L/d. Biogas production, gas composition, process stability parameters were measured. Results showed that with the pressure increasing from 0.3MPa to 1.7MPa, the pH value decreased from 7.22±0.19 to 6.98±0.05, the COD removal decreased from 93.0±0.9% to 79.7±1.2% and the methane content increased from 80.5±1.5% to 90.8±0.8%. Biogas with higher calorific value of 36.2MJ/m3 was obtained at a pressure of 1.7MPa. Pressure showed a significant effect on biogas production and gas quality in methanogenesis reactor.

Association Between Serum Fibroblast Growth Factor 21 and Mortality Among Patients With Coronary Artery Disease.

OBJECTIVES: Epidemiological studies have shown that serum fibroblast growth factor 21 (FGF21) levels were elevated in obesity and its related metabolic disorders. This prospective study assessed whether there was an independent association of serum FGF21 levels with all-cause and cardiovascular disease (CVD) mortality among patients with coronary artery disease (CAD). METHODS: A prospective cohort study of 1668 CAD patients was conducted. Their serum FGF21 levels were measured with ELISA kits. Cox regression models were used to estimate the association of serum FGF21 levels with the risk of mortality. RESULTS: During a median follow-up of 4.9 years, there were 194 deaths recorded and 130 of them were CVD deaths. Serum FGF21 levels positively correlated with age, body mass index, waist circumference, and adverse lipid profiles. Spline plots displayed a U-shaped association between serum FGF21 levels and all-cause as well as CVD mortality among CAD patients. Compared with serum FGF21 quartile 2, groups at quartiles 1, 3, and 4 had higher risk for all-cause and CVD mortality. Patients in the serum FGF21 quartile 4 had a 1.95-fold (95% confidence interval 1.25-3.02) risk of all-cause mortality and a 2.50-fold (95% confidence interval 1.43-4.38) risk of CVD mortality compared with those in quartile 2. CONCLUSIONS: The present study is the first to demonstrate that both higher and lower serum FGF21 levels were associated with increased risks for all-cause and CVD mortality, independent of traditional CVD risk factors.

MicroRNA-206 and its down-regulation of Wilms'Tumor-1 dictate podocyte health in adriamycin-induced nephropathy.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a frequent and severe glomerular disease characterized by destabilization of podocyte foot processes. Emerging evidence suggests that microRNAs play crucial roles in podocyte homeostasis. The aim of the present study was to determine the role of miR-206 in podocyte injury and to elucidate the mechanisms responsible for the damage to podocyte. METHODS: FSGS nephropathy model was induced by a single intravenous injection of Adriamycin (ADR) in BALB/c mice and the levels of proteinuria were measured on week of 1,3,5. The conditionally immortalized mouse podocyte cell line 5 was either transfected with microRNA mimics or negative control. Real-time PCR analysis was conducted to demonstrate the microRNA level in the glomeruli. Expression of Wilms' tumor-1 (WT1) and synaptopodin were detected by immunofluorescence and western blotting. RESULTS: The results revealed that miR-206 was up-regulated in ADR nephropathy mice, which led to severe podocyte injury and inhibited the expression of WT1 and synaptopodin. Using luciferase reporter assays, WT1 was identified as a target gene of miR-206. In vitro, over expression of miR-206 induced WT1 and synaptopodin degradation and actin rearrangement, initiating a catastrophic collapse of the entire podocyte-stabilizing system. CONCLUSIONS: Over expression of miR-206 promotes podocyte injury via downregulation of WT1, which provides a new pathogenic mechanism for FSGS and miR-206 may be a potential therapeutic target.

Body Mass Index, High-Sensitivity C-Reactive Protein and Mortality in Chinese with Coronary Artery Disease.

BACKGROUND: To investigate single and joint associations of body mass index (BMI) and serum high-sensitivity C-reactive protein (hsCRP) with death. METHODS: The study included 1871 coronary artery disease (CAD) patients aged 40-85 year-old recruited from 2008 to 2011. Cox regression models were used to estimate the association of BMI and hsCRP with mortality. The data was analyzed in 2014. RESULTS: During 3.1 years follow-up, 141 deaths were recorded, 110 died of cardiovascular disease (CVD). After adjustment of major CVD risk factors, there was a J-shaped association between BMI and all-cause and CVD mortality, and a positive association between hsCRP and mortality. The J-shaped association of BMI with mortality was present among patients who never smoked or with elevated hsCRP (≥3.0 mg/L). Compared with overweight (BMI 24-27.9 kg/m2) patients with normal hsCRP (<3.0 mg/L), obese patients (BMI≥28 kg/m2) with elevated hsCRP had a 3.41-fold risk of all-cause mortality (95% CI 1.49-7.80) and a 3.50-fold risk of CVD mortality (1.40-8.75), lean patients (BMI<24 kg/m2) with elevated hsCRP concentration had a 2.54-fold risk of all-cause mortality (1.36-4.74) and a 2.36-fold risk of CVD mortality (1.19-4.70). CONCLUSIONS: The association pattern between baseline BMI and mortality changed among different baseline hsCRP concentrations, indicating that low-grade inflammation may be related to BMI and secondary prognosis of CAD.

Expression of CPEB4 in Human Glioma and Its Correlations With Prognosis.

CPEB4 plays an important role in cancer progression. However, the clinicopathological significance of CPEB4 expression to glioma and its expression levels in glioma tissues and cell lines are unknown. The present study investigated the potential prognostic value of CPEB4 for human glioma.Immunohistochemistry (IHC) was performed to examine the dynamics of CPEB4 expression in glioma and nonneoplastic brain tissues, and the expression of CPEB4 in cell lines and freshly prepared tissue samples was measured using Western blotting and real-time PCR.CPEB4 was highly expressed at the mRNA and protein levels in 4 glioma cell lines and in 4 freshly prepared glioma tissues. Immunohistochemical analysis demonstrated that CPEB4 expression in glioma tissue was higher than that in corresponding nonneoplastic brain tissue (P < 0.01). This high expression level was further increased in high-grade gliomas, and the CPEB4 expression level correlated with the WHO classification (r = 0.774, P < 0.01). Moreover, the overall survival of glioma patients displaying high CPEB4 protein expression (P < 0.01) was clearly lower than that of those displaying low CPEB4 expression, and the high CPEB4 expression indicated a poorer survival in high-grade glioma patients (P < 0.01).Our study suggests that CPEB4 is significantly expressed in human glioma and that the upregulation of CPEB4 protein is significantly associated with advanced WHO grade. CPEB4 may serve as a highly sensitive prognostic indicator for glioma patients.