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Objective Systemic inflammation contributes to cardiovascular disease in patients with type 2 diabetes, and elevated white blood cell (WBC) counts are an established risk factor. Our goal is to describe changes in WBCs and inflammatory markers after glycemic reductions in diabetes. Research design and methods This study enrolled 63 subjects with poorly controlled diabetes, defined as hemoglobin A1c (HbA1c) ≥8% [64 mmol/mol]. Circulating granulocytes and mononuclear cells were separated by histopaque double-density protocol. Inflammatory markers from these isolated WBCs were assessed at baseline and after 3 months of medical management. Results After 3 months, significant glycemic reduction, defined as a decrease in HbA1c ≥ 1.5%, occurred in 42 subjects. Fasting plasma glucose decreased by 47% (165.6 mg/dL), and HbA1c decreased from 10.2 ± 1.8 to 6.8 ± 0.9. Glycemic reductions were associated with a 9.4% decrease in total WBC counts, 10.96% decrease in neutrophils, and 21.74% decrease in monocytes. The mRNA levels of inflammatory markers from granulocytes and mononuclear cells decreased, including receptor for advanced glycation endproducts; S100 calcium binding proteins A8, A9, A12; kruppel-like factor 5; and IL-1. Also, circulating levels of IL-1β and C-reactive protein decreased. Insulin dose was a mediator between HbA1c and both total WBC and neutrophil counts, but not changes in WBC inflammatory markers. In contrast, the 17 subjects without significant glycemic reductions showed no significant differences in their WBC counts and proteins of inflammatory genes. Conclusion Significant glycemic reduction in subjects with poorly controlled diabetes led to reduced circulating WBC counts and inflammatory gene expression.

BACKGROUND This study analyzed the risk factors of cognitive impairment (CI) in elderly patients with chronic diseases. MATERIAL AND METHODS In total of 385 elderly patients with chronic diseases were selected and assigned into CI and normal groups. The activities of daily living (ADL), global deterioration scale (GDS), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), patient-generated subjective global assessment (PG-SGA), and mini nutritional assessment (MNA) were performed to analyze the differences between the 2 groups. Logistic regression analysis was conducted for risk factors of CI in elderly patients with chronic diseases. RESULTS There were differences in age, education level, type 2 diabetes mellitus, multifocal cerebral infarction, hearing, and eyesight between CI and normal groups. Patients in the CI group showed more CD4+ cells, more admission times, and higher GDS scores than the normal group. Also, MMSE and MoCA scores revealed differences in total score, directive force, attention and calculating ability, language, delayed memory, reading comprehension, writing, and visual-spatial ability between the 2 groups. The number of B and CD8+ cells, ADL, and MNA scores were protective factors, while cerebral infarction history, number of CD4+ cells, admission times, GDS score, and age were risk factors of CI in elderly patients with chronic diseases. CONCLUSIONS Our study provides evidence that cerebral infarction history, number of CD4+ cells, admission times, GDS score, and age are risk factors of CI in elderly patients with chronic diseases.

MicroRNAs were known to play very important roles in human diseases, and have attracted great interests of research scientists in medicine, toxicology and functional foods. Gastric carcinoma (GC) remains one of the most common and lethal types of malignancy worldwide. However, the molecular mechanism of GC and the role of microRNAs in GC development remain unclear. The expression of extracellular matrix protein 1 (ECM1) is up-regulated in many cancer types, but its functional role is inconstant. In the present study, we aimed to investigate the correlation between GC development and ECM1 expression, along with its regulation by microRNAs. Immunohistochemical results showed that ECM1 was up-regulated in GC tissues and ECM1 expression level was negatively correlated with the prognosis of GC. ECM1 was found to promote gastric cancer cell metastasis in cell migration assays by facilitating the expression of proteins involved in epithelial-mesenchymal transition (EMT). MiR-92a was recognized for the first time to suppress the migration of human GC cells by directly targeting to the 3'UTR of ECM1 gene in a dual-luciferase reporter assay. These results highlighted the antagonistic roles of ECM1 and miR-92a in GC development, which may serve as a new target for gastric cancer.

The aim of the study was to investigate the correlation between the serum undercarboxylated osteocalcin (ucOC) level and the blood biochemistry and cognitive impairment in rats with type 2 diabetes mellitus (T2DM). Sprague-Dawley (SD) rats were randomly divided into the normal control group (NC) and type 2 DM group. DM group received the high-fat and high-sugar diet combined with the intraperitoneal injection of low-dose STZ to establish the type 2 DM rat model. After 12 weeks of feeding, a Morris water maze was used to observe the rats' cognitive ability, and the levels of blood lipid, ucOC, insulin and adiponectin in the two groups were measured. The results showed that blood glucose of rats in DM group was increased significantly at 2-12 weeks (p

Background and Aims Human epidermal growth factor receptor (EGFR) and HER2 (ErbB2) both belong to EGFR family, which are overexpressed in a significant proportion of cases of gastric cancer (GC). Various studies have evaluated the prognostic value of EGFR or HER level in GC. However, the overall test performance remains unclear. We undertook this study to perform a systematic review and meta-analysis of prognostic cohort studies evaluating the use of EGFR or HER2 as a predictor of survival time in patients with GC. Methods Eligible studies were identified through multiple search strategies. Studies were assessed for quality using the Newcastle–Ottawa Tool. Data were collected comparing overall survival (OS) in patients with high and low EGFR or HER2 level. Studies were pooled and summary hazard ratios were calculated. Results Studies were listed twice if they provided overall survival data for both EGFR and HER2. Eight studies (seven for EGFR and eight for HER2) were included. Two distinct groups were pooled for analysis and revealed that high EGFR, HER2 levels predicted poor overall (HR = 1.66, 95% CI: 1.35–2.02) and (HR = 1.43, 95% CI: 1.09–1.88) survival. No publication bias was found. Conclusions This meta-analysis result suggested that EGFR or HER2 should have significant predictive ability for estimating overall survival in GC patients and may be useful for defining prognosis of GC patients.

Effect of different strain rate on mechanical properties and microstructures of Fe-Mn-C twip steel were studied by dynamic compressed using Gleeble 3500 at room temperature. The results show that Rm and Rp0.2 gradually increase with the strain rate increasing, and the TWIP steel has a strong strain rate effect; The curves of strain hardening rate and true strain have different stage with different strain rate; The mechanism of the deformation behavior was also investigated, it was found that the evolution of microstructure was controlled by dislocation and deformation twins, but the density of dislocation and the appearance of twins were different with increasing strain rate.

Objectives Paclitaxel (PTX) is frequently used in the clinical treatment of solid tumors. But the PTX-resistance is a great obstacle in cancer treatment. Exploration of the mechanisms of drug resistance suggests that tumor suppressor genes (TSGs) play a key role in the response of chemotherapeutic drugs. TSGs, a set of genes that are often inactivated in cancers, can regulate various biological processes. In this study, an overview of the contribution of TSGs to PTX resistance and their underlying relationship in cancers are reported by using GeneMANIA, a web-based tool for gene/protein function prediction. Methods Using PubMed online database and Google web site, the terms “paclitaxel resistance” or “taxol resistance” or “drug resistance” or “chemotherapy resistance”, and “cancer” or “carcinoma”, and “tumor suppressor genes” or “TSGs” or “negative regulated protein” or “antioncogenes” were searched and analyzed. GeneMANIA data base was used to predict gene/protein interactions and functions. Results We identified 22 TSGs involved in PTX resistance, including BRCA1, TP53, PTEN, APC, CDKN1A, CDKN2A, HIN-1, RASSF1, YAP, ING4, PLK2, FBW7, BLU, LZTS1, REST, FADD, PDCD4, TGFBI, ING1, Bax, PinX1 and hEx. The TSGs were found to have direct and indirect relationships with each other, and thus they could contribute to PTX resistance as a group. The varied expression status and regulation function of the TSGs on cell cycle in different cancers might play an important role in PTX resistance. Conclusion A further understanding of the roles of tumor suppressor genes in drug resistance is an important step to overcome chemotherapy tolerance. Tumor suppressor gene therapy targets the altered genes and signaling pathways and can be a new strategy to reverse chemotherapy resistance.

Diacylglycerol acyl transferase 1 (DGAT1) catalyzes the final step in triglyceride (TG) synthesis, the conversion of diacylglycerol (DAG) to TG. Dgat1-/- mice exhibit a number of beneficial metabolic effects including reduced obesity and improved insulin sensitivity and no known cardiac dysfunction. In contrast, failing human hearts have severely reduced DGAT1 expression associated with accumulation of DAGs and ceramides. To test whether DGAT1 loss alone affects heart function we created cardiomyocyte specific DGAT1 knockout (hDgat1-/-) mice. hDgat1-/- mice hearts had 95% increased DAG and 85% increased ceramides compared to floxed controls. 50% of these mice died by 9 months of age. The heart failure marker brain natriuretic peptide (Bnp) increased 5-fold in hDgat1-/- hearts and fractional shortening (FS) was reduced. This was associated with a 30% increase in PPARalpha and a 40% increase in Cd36. We crossed hDgat1-/- mice with previously described enterocyte-specific Dgat1 knockout mice (hiDgat1-/-). This corrected the early mortality, improved FS 40%, and reduced cardiac ceramide and DAG content. Treatment of hDgat1-/- mice with GLP-1 receptor agonist exenatide for 1 week reduced Bnp mRNA by 50%, improved FS, and reduced heart DAG and ceramide content by 30-40%. Increased fatty acid uptake into hDgat1-/- hearts was normalized by exenatide. Reduced activity of protein kinase Cα (PKCα), which is known to be increased by DAG and ceramides, paralleled the reductions in these lipids. Our mouse studies show that loss of DGAT1 reproduces the lipid abnormalities seen in severe human heart failure.

Diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in triglyceride synthesis, the conversion of diacylglycerol (DAG) to triglyceride. Dgat1(-/-) mice exhibit a number of beneficial metabolic effects including reduced obesity and improved insulin sensitivity and no known cardiac dysfunction. In contrast, failing human hearts have severely reduced DGAT1 expression associated with accumulation of DAGs and ceramides. To test whether DGAT1 loss alone affects heart function, we created cardiomyocyte-specific DGAT1 knock-out (hDgat1(-/-)) mice. hDgat1(-/-) mouse hearts had 95% increased DAG and 85% increased ceramides compared with floxed controls. 50% of these mice died by 9 months of age. The heart failure marker brain natriuretic peptide increased 5-fold in hDgat1(-/-) hearts, and fractional shortening (FS) was reduced. This was associated with increased expression of peroxisome proliferator-activated receptor α and cluster of differentiation 36. We crossed hDgat1(-/-) mice with previously described enterocyte-specific Dgat1 knock-out mice (hiDgat1(-/-)). This corrected the early mortality, improved FS, and reduced cardiac ceramide and DAG content. Treatment of hDgat1(-/-) mice with the glucagon-like peptide 1 receptor agonist exenatide also improved FS and reduced heart DAG and ceramide content. Increased fatty acid uptake into hDgat1(-/-) hearts was normalized by exenatide. Reduced activation of protein kinase Cα (PKCα), which is increased by DAG and ceramides, paralleled the reductions in these lipids. Our mouse studies show that loss of DGAT1 reproduces the lipid abnormalities seen in severe human heart failure.

To evaluate the effect and safety of low-dose aspirin for primary prevention of cardiovascular events.We searched for randomized controlled trials (RCT) in the following electronic databases: MEDLINE, EMbase, the Cochrane Library (Issue 3, 2008), CBM, CNKI. Quality assessment and data extraction were conducted by two reviewers independently. All data were analyzed using Review Manager 4.2.Six studies (TPT, HOT, PPP, WHS, POPADAD, J-PAD) involving a total of 72,466 participants met the inclusion criteria. Meta-analysis results showed that: (1) Compared with placebo, the incidences of total cardiovascular events (RR = 0.85, 95% CI: 0.80-0.92), stroke (RR = 0.87, 95% CI: 0.77-0.98), nonfatal stroke (RR = 0.81, 95% CI: 0.70-0.95) and transient ischemic attack (RR = 0.76, 95% CI: 0.64-0.90) were significantly lower in low-dose aspirin group than those in placebo control group (all P0.05). (2) Nonfatal myocardial infarction (RR = 0.89, 95% CI: 0.77-1.02), death from cardiovascular causes (RR = 0.98, 95% CI: 0.86-1.13) and death from any cause (RR = 0.95, 95% CI: 0.88-1.02) were similar between the 2 groups (all P0.05). (3) The risk of coronary heart disease was reduced in low-dose aspirin group in the elderly (RR = 0.81, 95% CI: 0.70-0.94, P0.05). (4) The risk of bleeding was higher in low aspirin group compared to placebo group (RR = 1.15, 95% CI: 1.12-1.18, P0.01).Low-dose aspirin use could reduce the incidences of total cardiovascular events, stroke, nonfatal stroke and transient ischemic attack but increase the risk of bleeding, the incidence of nonfatal myocardial infarction, death from cardiovascular causes and death from any cause was not affected by low-dose aspirin use. Low-dose aspirin use was also significantly reduced the risk of coronary heart disease in the elderly.

To investigate the effects of aging and the decreased glomerular filtration rate on the prevalence of anemia in elder receiving body check from urban area of Hefei, China.A total of 454760 years subjects received healthy examination in Healthy Center of Anhui Provincial Hospital from January 2005 to December 2007 were enrolled in this study. Anemia was defined as hemoglobin120 g/L in men or110 g/L in women.The prevalence of anemia in the subjects was 4.40% (95%CI: 3.83% - 5.05%) and significantly increased with the aging process and the decline of estimated glomerular filtration rate (eGFR). With logistic analyses, increasing age, female, decreased eGFR were major risk factors for anemia.The morbidity of anemia is 4.40% in old population receiving body check from urban area of Hefei, China. Aging and the decline of eGFR are the independent risk factors of anemia.

To study the chiral selectivity in vascular endothelial differentiation in drug resistant lung cancer cells induced by high-dose L- or D-methotrexate (MTX) enantiomer.Human lung cancer cells of the line A549 were co-cultured with high-dose (15 micromol/L) L- or D-MTX enantiomer so as to develop cancer cells resistant to MTX. MTT method was used to detect the drug resistant index. Flow cytometry was used to detect the expression of CD44, a transmembrane glycoprotein reflecting the migration ability of cells, CD31, a marker of vascular endothelium, and P-170 protein. Fifteen BALB/c nude mice were inoculated with the parent A549 cells, L-MTX-resistant A549 cells induced by L-MTX enantiomer, and D-MTX-resistant A549 cells induced by D-MTX enantiomer. Four weeks later the mice were killed to take out the tumor masses. Immunohistochemistry with CD34 staining was used to detect the microvascular density (MVD).The drug resistant index of the D-MTX induced drug resistant A549 cells was 20.1 +/- 2.3, significantly higher than that of the L-MTX-induced cells (12.4 +/- 1.2, P = 0.000). The CD44 positive rate of the D-MTX induced A549 cells was 97.0% +/- 0.9%, not significantly different from that of the L-MTX-induced A549 cells (96.7% +/- 1.4%, P = 0.544). The CD31 positive rate of the D-MTX induced A549 cells was 91.9% +/- 3.2%, significantly higher than that of the L-MTX-induced A549 cells (32.9% +/- 8.0%, P = 0.000). The P-170 protein positive rate of the parent cells was 85.5% +/- 4.6%, and the P-170 protein positive rate of the D-MTX-induced A549 cells was 87.0% +/- 8.9%, significantly higher than that of the L-MTX-induced cells (71.5% +/- 8.2%, P = 0.002). The MVD of the D-MTX-induced cells was 55.9 +/- 11.9, significantly higher than that of the L-MTX-induced cells (7.2 +/- 1.7, P = 0.000). MVD was significantly positively correlated with the CD31 level (r = 0.462, P = 0.007), and not correlated with P-170 protein and CD34 levels.The MTX enantiomers have different chiral selectivity on human lung cancer cell, D-MTX resistant cells shows a potential of differentiation from cancer cells to vascular endothelial cells. D-MTX is not be regarded just as a pollutant in the drug MTX, MTX with single enantiomer (L-MTX) should be selected clinically so as to decrease the side effects of D-MTX.

Global DNA hypomethylation in tumor tissue is a common characteristic in a variety of malignancies such as breast, colon, oral, lung, and blood cancers. A rapid and sensitive method has been developed for the determination of global DNA methylation in cells. Five substances--2'-deoxycytidine (dC), 5-methyl 2'-deoxycytidine (mdC), 2'-deoxyadenosine (dA), 2'-deoxythymidine (dT), and 2'-deoxyguanosine (dG)--were completely separated by high-performance capillary electrophoresis in 10 min. Intraday coefficient of variation was less than 1%, and interday coefficient of variation was less than 2%. The minimal detection limit was 1 microM. Acquired drug resistance to methotrexate (MTX) is one of the most serious problems in cancer chemotherapy. Under optimal conditions, we analyzed global DNA methylation levels in A549 and A549/MTX cells, and only 10(5) cells are needed to obtain reliable results. The percentage of 5-methyl-2'-deoxycytidine (5-mC) was 4.80+/-0.52% in A549 cells, and this decreased to 4.20+/-0.44% in A549/MTX cells. It was considered as statistically significant. This demonstrated that the mechanisms of acquired drug resistance to MTX might be concerned with DNA methylation.

To investigate the effect of amino acid parenteral nutritional (PN) support on serum tryptophan and melatonin in non-small cell lung cancer (NSCLC) patients receiving chemotherapy.Seventy-two patients with inoperable NSCLC were divided into three groups randomly: control group, 250 ml/d amino acids PN therapy group and 500 ml/d amino acids PN therapy group. The same NP (cisplatin + vinorelbine) chemotherapy was carried out in all the three groups. During three sessions of chemotherapy,amino acids PN therapy was given to the amino acids PN therapy groups. Serum tryptophan and melatonin concentration changes were assessed before and after chemotherapy.After chemotherapy the concentration of MT and Try were much lower than that before chemotherapy in the three group patients (P0.05). But the concentration of MT and Try in the PN group patients was higher than that in control group patients. The concentration of MT and Try in the 500 ml/d amino acid parenteral nutritional support group patients were significantly higher than that in the 250 ml/d group patients, the difference was significant (P0.05).Amino acid parenteral nutritional support is beneficial to improve the lower concentration of serum MT and Try in NSCLC patients receiving chemotherapy, and a more significant effect can be achieved by the 500 ml/d amino acid parenteral nutritional support treatment.

Transcriptional silencing induced by CpG island methylation is believed to be one of the important mechanisms of carcinogenesis. Checkpoint with fork head-associated and ring finger (CHFR) governs the transition from prophase to prometaphase in response to mitotic stress. This study was to analyze the relationship between the methylation of CHFR gene and the clinicopathologic features of gastric cancer, and the difference of results between methylation-specific polymerase chain reaction (MSP) and combined bisulfite restriction analysis (COBRA) in detecting aberrant methylation of CHFR gene in gastric cancer.Both MSP and COBRA methods were used to detect the promoter methylation of CHFR gene in gastric cancer specimens from 64 patients. The relationship between methylation status of CHFR gene and the clinicopathologic features of gastric cancer were analyzed using SPSS16.0.The methylation rates of CHFR gene promoter were significantly higher in gastric cancer samples than in the corresponding paracancer normal gastric mucosa by MSP (51.6% vs. 18.8%, P0.001). However, there was no significant correlation between methylation status of CHFR gene and the clinicopathologic parameters of gastric cancer, including age, gender, tumor size, clinical stage, Borrman type, tumor invasion depth, differentiation, and lymph node metastasis (P0.05). Aberrant methylation of the CHFR gene was detected in 27 (42.2%) of the 64 specimens of gastric cancer using COBRA, which did not significantly differ from that using MSP (P0.05).Aberrant methylation of the CHFR gene is a frequent event in the carcinogenesis of gastric cancer. Detecting the methylation of CHFR gene in gastric mucosa may conduce to the diagnosis of gastric cancer. No difference was found between MSP and COBRA in detecting promoter methylation of CHFR gene in gastric cancer.