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.

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.

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.

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.

Association between serum interleukin-6 concentration and mortality in patients with coronary artery disease.

OBJECTIVES: To evaluate whether serum interleukin-6 (IL-6) is associated with increased risk of mortality in coronary artery disease (CAD) patients. METHODS: We performed a prospective cohort study of 718 CAD patients from the Guangzhou Cardiovascular Disease Cohort (GCDC) study. Multivariable-adjusted Cox proportional hazards regression analyses were used to examine the association between serum IL-6 with all-cause and cardiovascular mortality. RESULTS: During the 1663 person-years of followup, the cumulative all-cause mortality and cardiovascular mortality were 6.5% (n = 47) and 3.3% (n = 24), respectively. The mean length of followup was 2.32 ± 0.81 years. In the multivariable analyses, a one-SD increment in log-transformed serum IL-6 was positively associated with an increased risk of all-cause and cardiovascular mortality, with hazard ratios (HR) of 2.93 (95% CI, 2.11-4.08) and 2.04 (95% CI, 1.34-3.68) within the patients combined and 2.98 (95% CI, 2.12-4.18) and 3.10 (95% CI, 1.98-4.85) within males, respectively. Patients in the highest serum IL-6 tertile versus the lowest tertile were at higher risk of all-cause and cardiovascular mortality, with HR of 17.12 (95% CI 3.11-71.76) and 8.68 (95% CI, 1.88-37.51), respectively. CONCLUSIONS: In hospitalized patients with CAD, serum IL-6 is significantly associated with all-cause and cardiovascular mortality.

The prevalence and awareness of cardiometabolic risk factors in Southern Chinese population with coronary artery disease.

BACKGROUND: Cardiometabolic risk factors significantly accelerate the progression of coronary artery disease (CAD); however, whether CAD patients in South China are aware of the prevalence of these risk factors is not clear yet. METHODS: The study consisted of 2312 in-admission CAD patients from 2008 to 2011 in South China. Disease history including hypertension, dyslipidemia, and diabetes was relied on patients' self-reported records. Physical and clinical examinations were tested to assess the real prevalence of the cardiometabolic risk factors. RESULTS: 57.9% of CAD patients had more than 3 cardiometabolic risk factors in terms of the metabolic syndrome. The self-known and real prevalence of hypertension, diabetes, and dyslipidemia were 56.6%, 28.3%, and 25.1% and 91.3%, 40.9%, and 92.0%, respectively. The awareness rates were 64.4%, 66.3%, and 28.5% for hypertension, diabetes, and dyslipidemia. The prevalence of cardiometabolic risk factors was significantly different among gender and among disease status. CONCLUSIONS: Most CAD patients in South China had more than three cardiometabolic risk factors. However, the awareness rate of cardiometabolic diseases was low, especially for dyslipidemia. Strategies of routine physical examination programs are needed for the early detection and treatment of cardiometabolic risk factors in order to prevent CAD progression and prognosis.

Joint effects of genetic variants in multiple loci on the risk of coronary artery disease in Chinese Han subjects.

BACKGROUND: The aim of the present study was to explore risk variants for coronary artery disease (CAD) and to evaluate their joint effects (quantified by genetic risk score; GRS) on the discrimination of CAD in a Chinese Han sample. METHODS AND RESULTS: An association analysis of 91 single nucleotide polymorphisms (SNPs) with CAD risk was undertaken in 1,007 CAD patients and 889 healthy controls. Two GRSs, counted GRS (cGRS) and weighted GRS (wGRS), were calculated using the significant SNPs, and their discriminant power for CAD was assessed using receiver-operating characteristic (ROC) curve analysis. Eight SNPs (rs11206510, rs10118757, rs2383206, rs501120, rs2075292, rs174547, rs173539, and rs255052) were nominally significantly associated with CAD (P<0.05), and 5 of them were newly reported. The GRSs derived from the 8 SNPs improved the discrimination of CAD compared to that using 4 conventional risk factors (P=0.002 for cGRS and P=0.009 for wGRS). After 10-fold cross-validation 100 times, the average areas under the curve were 0.668 (95% confidence interval [CI]: 0.667-0.669), 0.686 (95% CI: 0.685-0.687) and 0.690 (95% CI: 0.689-0.691) for models with conventional risk factors only, conventional risk factors plus cGRS, and conventional risk factors plus wGRS, respectively. CONCLUSIONS: A multigenic GRS, generated by combining multiple gene variants, can improve discrimination of CAD, thereby confirming the joint effects of these gene variants on CAD in this Chinese Han population.

Lack of association between four SNPs in the SLC22A3-LPAL2-LPA gene cluster and coronary artery disease in a Chinese Han population: a case control study.

BACKGROUND: Lipoprotein (a) (Lp [a]) is known being correlated with coronary artery disease (CAD). The SLC22A3-LPAL2-LPA gene cluster, relating with modulating the level of plasma Lp (a), has recently been reported to be associated with CAD in Caucasians. The purpose of this study was to verify whether this finding can be expanded to the Chinese Han population. METHODS AND RESULTS: Using a Chinese Han sample, which consisted of 1012 well-characterized CAD patients and 889 healthy controls, we tested the associations of four SNPs (rs2048327, rs3127599, rs7767084 and rs10755578) in the SLC22A3-LPAL2-LPA gene cluster, and their inferred haplotypes with the risk of CAD. Allelic, genotypic and haplotype association analyses all showed that the gene cluster was not associated with CAD in this Chinese Han sample. CONCLUSIONS: We for the first time explored the association of the four SNPs in the SLC22A3-LPAL2-LPA gene cluster with CAD in a large Chinese Han sample. Nevertheless, this study did not reveal any significant evidence of this gene cluster to increase the risk of CAD in this population.

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.

Relationship between lipid profiles and plasma total homocysteine, cysteine and the risk of coronary artery disease in coronary angiographic subjects.

BACKGROUND: Homocysteine and cysteine are considered as risk factors of cardiovascular disease. Homocysteine influences the liver expression of ApoA-I and decreases its blood level and HDL in genetic mice model. We aimed therefore to evaluate whether homocysteine and cysteine are associated with lipid parameters, and the joint effects of them on the risk of coronary artery disease (CAD). Plasma total homocysteine (tHcy), cysteine (tCys) and lipid markers were measured in 2058 consecutive coronary artery angiographic patients. RESULTS: Plasma tHcy but not tCys correlated negatively with ApoA-I (r = -0.153, P < 0.001) and with HDL cholesterol (r = -0.148, P < 0.001), and correlated positively with the risk of CAD (OR: 1.61; 95% confidence interval; 1.26 to 2.05). Combination of high tHcy and high tCys levels was associated with decreased ApoA-I and HDL cholesterol levels, and with increased risk of CAD (OR: 1.696, 95% CI (1.301-2.211)). Furthermore, low HDL cholesterol combined with low tHcy or high tHcy all had increased risk for CAD (OR: 1.254, 95% CI (1.114-1.565); OR: 1.332, 95% CI (1.093-1.624); respectively) whereas high HDL cholesterol counteracted the harmful effect of high tHcy on the risk of CAD. However, only the combination of high tHcy and high ApoA-I had an increased risk for CAD (OR: 1.438, 95% CI (1.170-1.768)). CONCLUSIONS: The association of homocysteine and cysteine, ApoA-I or HDL cholesterol and their joint effects provide new insights on its role on CAD.

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.

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.

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.

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.

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.

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.

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.

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.