The mean reticulocyte volume is a valuable index in early diagnosis of cancer-related anemia.

Background: Cancer-related anemia (CRA) is a functional iron deficient anemia, and the early diagnosis will improve the prognosis of the patients. This prospective study aimed to investigate the utility of mean reticulocyte volume (MRV) in the early diagnosis of CRA. Methods: A total of 284 first-diagnosed cancer patients were enrolled, and the subjects were assigned anemia and non-anemia groups by hemoglobin (Hb) concentrations. The mature RBC and reticulocyte indices were detected with BC-7500 blood analyzer, and the MRV, reticulocyte hemoglobin (RHE) content, and reticulocyte production index (RPI) were obtained. ROC curves were constructed in identifying anemia diagnosed by the combination of RHE and RPI. An adjusted multivariate analyse and quartiles were used to assess the associations of MRV with early CRA diagnosed by combining RBC indices (MCV, MCH and MCHC), respectively. Results: No statistical differences were observed in MCV, RHE and MRV levels between anemia and non-anemia subjects (p > 0.05). MRV exhibited a complete or high correlation with the RHE levels (r = 1.000, p < 0.001), or MCV, MCH, and MCHC in anemia patients (R: 0.575-0.820, p < 0.001). ROC curves analyse indicated a highest area under curve of 0.829 (95% CI [0.762-0.895]) and 0.884 (95% CI [0.831-0.936]) for MRV in identifying anemia in male and female patients, respectively (p < 0.001). When the optimal cutoff values of MRV were set at 100.95 fl in males and 98.35 fl in females, the sensitivity and specificity were 1.00 and 0.68, and 1.00 and 0.73, respectively. The regression analyse showed that, when being as a categorical variable, MRV showed an odds ratio of 19.111 (95% CI [6.985-52.288]; p < 0.001) for the incidence of CRA. The incidence of overall anemia demonstrated a more significant decrease trend along with the increase of MRV quartiles (p-trend < 0.001). Conclusion: This study revealed that the MRV can be used as a convenient and sensitive index in early diagnosis of cancer-related anemia, and decreased MRV level may be the powerful predictor of overt anemia in cancer patients.

An AMPK agonist suppresses the progress of colorectal cancer by regulating the polarization of TAM to M1 through inhibition of HIF-1α and mTOR signal pathway.

OBJECTIVE: This study aimed to evaluate the impact of an adenosine monophosphate-activated protein kinase (AMPK) agonist, metformin (MET), on the antitumor effects of macrophages and to determine the underlying mechanism involved in the process. MATERIALS AND METHODS: M0 macrophages were derived from phorbol-12-myristate-13-acetate-stimulated THP-1 cells. RESULTS: The levels of tumor necrosis factor-alpha (TNF-α) and human leukocyte antigen-DR (HLA-DR) were decreased in macrophages incubated with HCT116 cells, whereas those of arginase-1 (Arg-1), CD163, and CD206 were elevated; these effects were reversed by MET. The transfection of small interfering (si) RNA abrogated the influence of MET on the expression of the M1/M2 macrophage biomarkers. MET significantly suppressed the proliferation and migration abilities of HCT116 cells incubated with M0 macrophages; these actions were reversed by siRNA transfection against AMPK. The hypoxia-inducible factor 1-alpha (HIF-1α), phosphorylated protein kinase B (p-AKT), and phosphorylated mammalian target of rapamycin (p-mTOR) levels were reduced by the introduction of MET and promoted by siRNA transfection against AMPK. In addition, the levels of HIF-1α, p-AKT, and p-mTOR suppressed by MET were markedly increased following the transfection of siRNA against AMPK. CONCLUSION: These findings indicate that MET can repress the progression of colorectal cancer by transforming tumor-associated macrophages to the M1phenotype via inhibition of the HIF-1α and mTOR signaling pathways.

Predictive significance of joint plasma fibrinogen and urinary alpha-1 microglobulin-creatinine ratio in patients with diabetic kidney disease.

BACKGROUND: Although many biomarkers have high diagnostic and predictive power for diabetic kidney disease (DKD), less studies were performed for the predictive assessment in DKD and its progression with combined blood and urinary biomarkers. This study aims to explore the predictive significance of joint plasma fibrinogen (FIB) concentration and urinary alpha-1 microglobulin-creatinine (α1-MG/CR) ratio in DKD. METHODS: A total of 234 patients with type 2 diabetes were enrolled, and their clinical and laboratory data were retrospectively assessed. A ROC curve analysis was performed to evaluate the power of plasma FIB and urinary α1-MG/CR ratio for identifying DKD and advanced DKD, respectively. The predictive power for DKD and advanced DKD was analyzed by regression analysis. RESULTS: Plasma FIB and urinary α1-MG/CR levels were higher in patients with DKD than with pure T2D (p<0.001). The multivariate-adjusted odds ratios (ORs) were 5.047 (95%CI: 2.276-10.720) and 2.192 (95%CI: 1.539-3.122) (p<0.001) for FIB and α1-MG/CR as continuous variables for DKD prediction, respectively. The optimal cut-off values were 3.21 g/L and 2.11mg/mmol for identifying DKD, and 5.58 g/L and 11.07 mg/mmol for advanced DKD from ROC curves. At these cut-off values, the sensitivity and specificity of joint FIB and α1-MG/CR were 0.95 and 0.92 for identifying DKD, and 0.62 and 0.67 for identifying advanced DKD, respectively. The area under curve was 0.972 (95%CI: 0.948-0.995) (p<0.001) and 0.611, 95%CI: 0.488-0.734) (p>0.05). The multivariate-adjusted ORs for joint FIB and α1-MG/CR at the cut-off values were 214.500 (95%CI: 58.054-792.536) and 3.252 (95%CI: 1.040-10.175) (p<0.05), respectively. CONCLUSION: The present study suggests that joint plasma FIB concentration and urinary α1-MG/CR ratio can be used as a powerful predictor for general DKD, but it is less predictive for advanced DKD.

The long non-coding RNA NNT-AS1 promotes clear cell renal cell carcinoma progression via regulation of the miR-137/ Y-box binding protein 1 axis.

Long noncoding RNAs (lncRNAs) have been implicated in the progression of malignant tumors, including in clear cell renal cell carcinoma (ccRCC). However, the function and the specific mechanism of lncRNA nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) in ccRCC remains unknown. Thus, this study explored the role of NNT-AS1 in ccRCC. We evaluated NNT-AS1 expression in ccRCC specimens. Next, CCK-8 and Transwell assays were used to evaluate cell proliferation and metastatic abilities. The interaction between miR-137 and NNT-AS1 or Y-box binding protein 1 (YBX-1) was confirmed using a dual luciferase reporter assay. The results showed that NNT-AS1 was significantly upregulated in ccRCC specimens compared with normal tissues. Inhibition of NNT-AS1 restrained ccRCC proliferation and metastasis. Mechanistically, NNT-AS1 acted as a competitive endogenous RNA to sponge miR-137, which depressed ccRCC cells proliferation and metastasis. Moreover, with the use of bioinformatics analysis, the famous oncogene YBX-1 was selected as the potential target of miR-137. Luciferase assay also confirmed the interaction between miR-137 and YBX-1. Further functional studies demonstrated that the inhibition effect of NNT-AS1 knockdown on ccRCC carcinogenesis could be partially reversed by overexpression of YBX-1, suggesting that NNT-AS1 promotes ccRCC progression through the miR-137/YBX-1 pathway. In summary, these findings indicate that NNT-AS1 promotes ccRCC progression via the miR-137/YBX-1 pathway, which may provide a promising therapeutic target for renal cell carcinoma.

Clinical and predictive significance of Plasma Fibrinogen Concentrations combined Monocyte-lymphocyte ratio in patients with Diabetic Retinopathy.

Diabetic retinopathy (DR) is one of the most common causes of blindness and visual impairment. Therefore, early prediction of its occurrence and progression is important. This study aimed to assess the clinical and predictive significance of plasma fibrinogen concentrations combined monocyte-lymphocyte ratio (FC-MLR) in patients with DR. A total of 307 patients with type 2 diabetes (T2D) were enrolled. Plasma fibrinogen concentrations and peripheral white blood cells were measured, and MLR was calculated, and the associations of FC-MLR with DR and severity of disease were assessed. Regression analysis and receiver operating characteristic (ROC) curves were performed to evaluate the risk factors and predictive power of FC-MLR for DR and severity of disease, respectively. DR patients showed higher fibrinogen concentrations and a higher MLR than did T2D patients without complications (P<0.01); Moreover, DR patients in proliferative stage also showed higher fibrinogen concentrations and a higher MLR than did those in non-proliferative stage (P<0.01). FC-MLR was closely associated with occurrence and severity of DR (P<0.01), and was an independent risk factor for them (OR=6.123, 95%CI: 3.122-17.102; and 7.932, 95%CI: 4.315-16.671, respectively; P<0.001). The predictive sensitivity and specificity for DR and severity of disease were 0.86 and 0.68, and 0.85 and 0.73, respectively. The study suggests that FC-MLR may be used as a predictor for the risk and progression of diabetic retinopathy.

Monocyte-lymphocyte ratio is a valuable predictor for diabetic nephropathy in patients with type 2 diabetes.

Diabetic nephropathy (DN) is serious threat to human health. Therefore, early prediction of its occurrence is important. This study aimed to assess the predictive significance of monocyte-lymphocyte ratio (MLR) for DN.A total of 301 patients with type 2 diabetes (T2D), including 212 T2D patients without diabetic-related complications and 99 DN patients, were enrolled. Peripheral white blood cells were measured before treatment to calculate MLR, and the risk factors and predictive significance for T2D and DN were assessed.T2D patients without diabetic-related complications had higher MLR than control patients (P < .01). However, MLR was significantly higher in DN patients than in T2D patients without diabetic-related complications (P < .001). According to MLR quartiles, higher MLR in DN patients was correlated with higher serum creatinine, estimated glomerular filtration rate, and urinary albumin excretion (UAE) levels (P < .01 or P < .001). Furthermore, MLR was positively correlated with UAE level (R = 0.5973; P < .01) and an independent predictor for DN (odds ratio: 7.667; 95% confidence interval [CI]: 3.689-21.312; P < .001). The area under the receiver-operating characteristic (ROC) curve for MLR was 0.874 (95%CI: 0.830-0.918, P < .001). When the optimal cutoff value was 0.23, the sensitivity and specificity of MLR for DN prediction were 0.85 and 0.74, respectively.The present findings suggest that MLR is a powerful independent predictor for DN.

Predicting significance of COX-2 expression of peripheral blood monocyte in patients with coronary artery disease.

BACKGROUND: Cyclooxygenase-2 (COX-2) plays an important role in the monocyte-platelet aggregate (MPA)-medicated inflammatory response and possible coronary artery disease (CAD). This study aimed to assess the predicting significance of COX-2 expression in peripheral blood monocyte for CAD. METHODS: A total of 66 patients with CAD including stable angina (SA) and unstable angina (UA) were enrolled. The inflammatory indexes including white blood cell (WBC) count, high-sensitive C reactive protein (hs-CRP), serum monocyte chemoattractant protein-1 (MCP-1) and MPA levels were measured. The western-blotting assay and reverse transcription-polymerase chain reaction (RT-PCR) analysis were used to detect the COX-2 expression in peripheral blood monocytes. Furthermore, the correlation between COX-2 expression and MPA levels, and the association of COX-2 expression with CAD risk were assessed. RESULTS: The UA patients demonstrated higher levels of inflammatory indexes than the SA patients (P<0.001). Simultaneously, higher MPA levels and enhanced COX-2 expression were observed in the UA patients (P<0.01). The patients with enhanced COX-2 expression exhibited higher MPA than those without (P<0.01), and patients with increased MPA also demonstrated enhanced COX-2 expression (P<0.001). Moreover, the levels of COX-2 protein expression was positively related to the MPA formation rates (R2=0.4933, P<0.01), and enhanced COX-2 expression was independently associated with CAD risk [odds ratio (OR): 6.322, 95% confidence interval (CI): 4.544-8.978 ]. CONCLUSIONS: The COX-2 expression of peripheral blood monocytes can be used as an independent predictor for CAD.

Thyroid stimulating hormone and free triiodothyronine are valuable predictors for diabetic nephropathy in patient with type 2 diabetes mellitus.

BACKGROUND: Diabetes seriously threatens human health, and diabetic nephropathy (DN) is one of the serious diabetic complications. Therefore, it is valuable to predict the occurrence of DN early. This study aims to evaluate the predicting significance of thyroid hormones for DN. METHODS: A total of 301 type 2 diabetes mellitus (T2DM) patients were enrolled. Thyroid hormones before treatment were measured, and the risk factors and their predicting significance for T2DM and DN were assessed. RESULTS: The results indicated that there was no statistical difference in any investigated variable between controls and patients without complications (P>0.05). However, patients with DN exhibited lower levels of triiodothyronine (T3) and free triiodothyronine (FT3), but higher levels of thyroid stimulating hormone (TSH) than T2DM patients without complications (P<0.001). Multivariate analysis did not demonstrate any thyroid hormone as the independent risk factor for T2DM without complications, but revealed increased TSH and decreased T3 and FT3 as the independent risk factors for patients with DN [odds ratio (OR): 2.087, 95% CI: 1.525-3.303; 1.335, 95% CI: 1.101-1.621; 7.414, 95% CI: 4.319-13.986; P<0.001, respectively]. The area under receiver operating characteristic (ROC) curve of TSH, FT3 and T3 was 0.850 (95% CI: 0.776-0.923), 0.824 (95% CI: 0.751-0.897), and 0.620 (95% CI: 0.515-0.725) for DN prediction. Based on their cutoff values of 1.85 mIU/L, 2.31 ng/L, and 0.61 µg/L, the sensitivity was 82%, 78%, and 64%, and the specificity was 77%, 79%, and 85%, respectively. CONCLUSIONS: Our findings suggest that TSH and FT3 are useful predictors for DN in patients with T2DM.

Clinical Significance of Hemostatic Parameters in the Prediction for Type 2 Diabetes Mellitus and Diabetic Nephropathy.

It would be important to predict type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). This study was aimed at evaluating the predicting significance of hemostatic parameters for T2DM and DN. Plasma coagulation and hematologic parameters before treatment were measured in 297 T2DM patients. The risk factors and their predicting power were evaluated. T2DM patients without complications exhibited significantly different activated partial thromboplastin time (aPTT), platelet (PLT), and D-dimer (D-D) levels compared with controls (P < 0.01). Fibrinogen (FIB), PLT, and D-D increased in DN patients compared with those without complications (P < 0.001). Both aPTT and PLT were the independent risk factors for T2DM (OR: 1.320 and 1.211, P < 0.01, resp.), and FIB and PLT were the independent risk factors for DN (OR: 1.611 and 1.194, P < 0.01, resp.). The area under ROC curve (AUC) of aPTT and PLT was 0.592 and 0.647, respectively, with low sensitivity in predicting T2DM. AUC of FIB was 0.874 with high sensitivity (85%) and specificity (76%) for DN, and that of PLT was 0.564, with sensitivity (60%) and specificity (89%) based on the cutoff values of 3.15 g/L and 245 × 109/L, respectively. This study suggests that hemostatic parameters have a low predicting value for T2DM, whereas fibrinogen is a powerful predictor for DN.

Tissue Factor Pathway Inhibitor-1 Is a Valuable Marker for the Prediction of Deep Venous Thrombosis and Tumor Metastasis in Patients with Lung Cancer.

Activation of blood coagulation contributes to cancer progression. Tissue factor pathway inhibitor-1 (TFPI-1) is the main inhibitor of extrinsic coagulation pathway. The aim of this study is to assess the predicting significance of TFPI-1 for thrombotic complication and metastasis in lung cancer patients. Total of 188 non-small cell lung cancer (NSCLC) patients were included in this study. Plasma TFPI-1, D-dimer (D-D), antithrombin (AT), Fibrinogen (Fbg), and coagulating factor VIII activity (FVIII:C) were measured. In NSCLC patients, significantly decreased TFPI-1 and AT and increased D-D, Fbg, and FVIII:C levels were observed, and there was a significant correlation between TFPI-1 and other hemostatic parameters (P < 0.001, resp.). NSCLC patients with deep venous thrombosis (DVT) or metastasis had significantly lower TFPI-1 levels than those without DVT or metastasis (P < 0.01, resp.). Multivariate regression revealed that TFPI-1 acted as a predictor for DVT or tumor metastasis in NSCLC patients [OR: 4.15 or 3.28, P < 0.05, resp.]. The area under ROC curve of TFPI-1 was 0.905 (95% CI, 0.842~0.967) or 0.828 (95% CI, 0.742~0.915) for predicting DVT or metastasis (P < 0.001, resp.). The optimal point of TFPI-1 was 57.7 or 54.3 ng/mL for predicting DVT or metastasis, respectively. Combination of TFPI-1 and D-D measurements can improve the predicting power for DVT or metastasis in NSCLC patients. Our findings suggested that TFPI-1 was a valuable predictor of DVT and tumor metastasis in NSCLC patients.

Association of HLA-DQA1 (rs9272219) with susceptibility to rheumatoid arthritis in a Han Chinese population.

HLA-DQA1 (rs9272219) has been previously reported that it is a susceptibility locus in rheumatoid arthritis (RA) of UK Caucasian population and North American; however, it has not reported in RA of Chinese population. Our study was to identify whether or not this relationship is reside between rs9272219 and RA in a Han Chinese population. 207 patients with RA and 199 control subjects were recruited. The single nucleotide polymorphism (SNP) of rs9272219 was tested in alleles and genotype frequencies and the data was analyzed by doing the statistic analysis of odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses after pairwise linkage disequilibrium (LD) was estimated. Finally, the Alleles and genotype frequencies distribution of rs9272219 locus among RA patients and control subjects were in accordance with Hardy-Weinberg equilibrium. We found significant association between rs9272219 and RA of Chinese population (OR 0.494, 95% confidence interval [95% CI] 0.354-0.688, P = 0 and OR 2.541, 95% CI 1.695-3.808, P = 0, respectively). In this study, we found that the SNP of rs9272219 in HLA-DQA1 is a potential susceptibility locus in RA of Han Chinese population; the results suggest that HLA-DQA1 may be related to the development of RA.

TNFAIP3 rs2230926 polymorphisms in rheumatoid arthritis of southern Chinese Han population: a case-control study.

Polymorphism of tumor necrosis factor alpha-induced protein 3 (TNFAIP3) has been be related to various auto-immune diseases. Based on previous studies that the single nucleotide polymorphism (SNP) of rs2230926 was association with rheumatoid arthritis (RA) of Japanese, Caucasian population and the northern Chinese Han population, we tested the alleles and geno-type frequencies of rs2230926 in TNFAIP3 to investigate whether rs2230926 is susceptible to RA of southern Chinese Han population. In our case-control association study, 207 RA patients fulfilling the American College of Rheumatology (ACR) 1987 criteria were compared with 199 unrelated healthy subjects. After testing the alleles and genotype frequencies of rs2230926, the airwise linkage disequilibrium (LD) was computed and odd ration (OR) and 95% confidence intervals (95% CI) were used for evaluating the susceptibility to RA. The SNP of rs2230926 of the cases and control subjects were conformed to the Hardy-Weinberg equilibrium (P = 0.02257). The significantly statistical differences in alleles of T, G were founded in the cases and controls (P = 0.0027, OR 0.417, 95% CI 0.232-0.749); the genetic types of rs2230926 were associated with a susceptibility to RA, with OR 0.375 (95% CI 0.198-0.707, P = 0.0018). In the present study, our results indicated that the genetic polymorphism of rs2230926 in TNFAIP3 may be a susceptible factor conferring risk for RA in southern Chinese Han population.