Predictive value of bone turnover markers and thyroid indicators for bone metabolism in GD patients after treatment.

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively. Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered. Results: The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05). Conclusion: BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.

Clinical evaluation of a multitarget fecal immunochemical test-sDNA test for colorectal cancer screening in a high-risk population: a prospective, multicenter clinical study.

Colorectal cancer (CRC) is a major malignancy threatening the health of people in China and screening could be effective for preventing the occurrence and reducing the mortality of CRC. We conducted a multicenter, prospective clinical study which recruited 4,245 high-risk CRC individuals defined as having positive risk-adapted scores or fecal immunochemical test (FIT) results, to evaluate the clinical performance of the multitarget fecal immunochemical and stool DNA (FIT-sDNA) test for CRC screening. Each participant was asked to provide a stool sample prior to bowel preparation, and FIT-sDNA test and FIT were performed independently of colonoscopy. We found that 186 (4.4%) were confirmed to have CRC, and 375 (8.8%) had advanced precancerous neoplasia among the high CRC risk individuals. The sensitivity of detecting CRC for FIT-sDNA test was 91.9% (95% CI, 86.8-95.3), compared with 62.4% (95% CI, 54.9-69.3) for FIT (P < 0.001). The sensitivity for detecting advanced precancerous neoplasia was 63.5% (95% CI, 58.3-68.3) for FIT-sDNA test, compared with 30.9% (95% CI, 26.3-35.6) for FIT (P < 0.001). Multitarget FIT-sDNA test detected more colorectal advanced neoplasia than FIT. Overall, these findings indicated that in areas with limited colonoscopy resources, FIT-sDNA test could be a promising further risk triaging modality to select patients for colonoscopy in CRC screening.

MPs-ACT, an Assay to Evaluate the Procoagulant Activity of Microparticles.

The procoagulant effect of microparticles (MPs) contributes to hypercoagulability-induced thrombosis. We provide preliminary findings of the MPs-Activated Clotting Time (MPs-ACT) assay to determine the procoagulant activity of MPs. MPs-rich plasma was obtained and recalcified. Changes in plasma viscoelasticity were evaluated and the time to the peak viscoelastic changes was defined as the MPs-ACT. MPs concentration was measured by flow cytometry. Coagulation products produced during plasma clotting were identified by fibrin and fibrinopeptide A. MPs were prepared in vitro and added to standard plasma to simulate pathological samples. In addition, reproducibility and sensitivity were evaluated. We confirmed the linear relationship between MPs-ACT and MP concentrations. Dynamic changes in fibrin production were depicted. We simulated the correlation between MPs-ACT and standard plasma containing MPs prepared in vitro. The reproducibility of high-value and low-value samples was 6.0% and 10.8%, respectively. MPs-ACT sensitively detected hypercoagulable samples from patients with pre-eclampsia, hip fractures, and lung tumors. MPs-ACT largely reflects the procoagulant effect of MPs. MPs-ACT sensitively and rapidly detects hypercoagulability with MPs-rich plasma. It may be promising for the diagnosis of hypercoagulable states induced by MPs.

Elevated expression of the MYB proto-oncogene like 2 (MYBL2)-encoding gene as a prognostic and predictive biomarker in human cancers.

Recently, MYBL2 is frequently found to be overexpressed and associated with poor patient outcome in breast cancer, colorectal cancer, bladder carcinoma, hepatocellular carcinoma, neuroblastoma and acute myeloid leukemia. In view of the fact that there is an association between MYBL2 expression and the clinicopathological features of human cancers, most studies reported so far are limited in their sample size, tissue type and discrete outcomes. Furthermore, we need to verify which additional cancer entities are also affected by MYBL2 deregulation and which patients could specifically benefit from using MYBL2 as a biomarker or therapeutic target. We characterized the up-regulated expression level of MYBL2 in a large variety of human cancer via TCGA and oncomine database. Subsequently, we verified the elevated MYBL2 expression effect on clinical outcome using various databases. Then, we investigate the potential pathway in which MYBL2 may participate in and find 4 TFs (transcript factors) that may regulate MYBL2 expression using bioinformatic methods. At last, we confirmed elevated MYBL2 expression can be useful as a biomarker and potential therapeutic target of poor patient prognosis in a large variety of human cancers. Additionally, we find E2F1, E2F2, E2F7 and ZNF659 could interact with MYBL2 promotor directly or indirectly, indicating the four TFs may be the upstream regulator of MYBL2. TP53 mutation or TP53 signaling altered may lead to elevated MYBL2 expression. Our findings indicate that elevated MYBL2 expression represents a prognostic biomarker for a large number of cancers. What's more, patients with both P53 mutation and elevated MTBL2 expression showed a worse survival in PRAD and BRCA.

One potential hotspot ACADVL mutation in Chinese patients with very-long-chain acyl-coenzyme A dehydrogenase deficiency.

Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCAD deficiency), a rare autosomal recessive disorder, is characterized by hypoketotic hypoglycemia, cardiomyopathy, liver damage, and myopathy. VLCAD deficiency is caused by defects of ACADVL gene, which encodes VLCAD protein. The aim of this study was to determine the clinical, biochemical, prognosis and mutation spectrum of patients with VLCAD deficiency in mainland China. A total of Six families visited us, four patients (2 boys and 2 girls) were admitted in hospital due to liver dysfunction, hypoglycemia, and positive newborn screen result. The parents of the other two patients (2 girls) visited us for genetic consultation after their children's death. All the six patients had elevated level of serum tetradecenoylcarnitine (C14:1-carnitine), four of them showed decreased free carnitine (C0) level, and three had dicarboxylic aciduria. Eight types of mutations of the ACADVL gene were detected, three of them are novel, including c.563G > A (p.G188D) c.1387G > A (p.G463R) and c.1582_1586del (p.L529Sfs*31). The p.R450H mutation accounts for 9/52 alleles (5/40 in previous study of 20 unrelated patients, and 4/12 in this study) of genetically diagnosed Chinese VLCAD deficiency cases. The four alive patients (Patient 1-4) responded well to diet prevention and drug therapy with stable hepatic dysfunction condition. In conclusion, we describe three novel mutations of the ACADVL gene among six unrelated families with VLCAD deficiency. Moreover, we suggest that the p.R450H may be a potential hotspot mutation in the Chinese population.

Early changes in gene expression of the entire pathological process in Cutaneous T-cell lymphoma.

In this study, we aimed to explore the time-course relating to the pathological progression of Cutaneous T-cell lymphoma (CTCL) and to identify the early changes in gene expression. The raw microarray data of CTCL was downloaded from the Gene Expression Omnibus database and a weighted gene coexpression network analysis was performed. A total of 2183 genes that positively correlated with the time course of CTCL development were identified in as part of the turquoise module as well as 1096 genes negatively correlated with the time course of CTCL development, which was identified in the blue module. To better understand the effects of these genes on prognosis, we further performed the Spearman correlation analysis, univariate Cox regression analysis, and Kaplan-Meier survival analysis. We identified 10 differentially expressed genes whose expression was significantly associated with prognosis in patients with CTCL. Our findings can help our understanding of the underlying mechanisms of CTCL as well as the development of novel drugs.

Early Stage Biomarkers Screening of Prostate Cancer Based on Weighted Gene Coexpression Network Analysis.

Although the morbidity and mortality rates of prostate cancer (PCa) are considerably high, many PCas are characterized as indolent and slow growing, which do not require overtreatment. Overdiagnosis and overtreatment of early detected PCa are an emerging problem, owing to a lack of biomarkers that detect advanced disease at an earlier stage. In this study, RNA-Seq data of 57,045 genes for 495 PCa samples and 52 normal samples in the The Cancer Genome Atlas (TCGA) database were downloaded. Subsequently, we performed weighted gene coexpression network analysis to identify the Gleason score-related coexpression gene module, and further screened out oncogenes and tumor suppressors that were upregulated or downregulated in the early stage of PCa as well as those related to the clinical prognosis of PCa patients. Based on this study, some novel biomarkers were identified for the disease-free survival, which are helpful for fast diagnosis and prognosis.

Long Period and High Level of D-Dimer after Coronary Artery Bypass Grafting Surgery.

Hyper-coagulation after off-pump coronary artery bypass grafting (OPCAB) is one of the main reasons for graft thrombosis. D-dimer is closely linked to the activation of coagulation. Few studies have reported the variation range and long-term abnormal coagulation after OPCAB in the Chinese population. Our study aimed to determine the characteristics and value of D-dimer after OPCAB.In this prospective study, 265 patients who underwent OPCAB for the first time were recruited from 2011 to 2012. The D-dimer level of the patients was tested before surgery and on the 1st, 4th, and 14th day, and 1st, 2nd, and 3rd month after surgery. Clinical data in the perioperative period and during the one-year follow-up period were recorded.D-dimer level increased from day 4 after OPCAB ([1321.9 ± 36.4] µg/L), peaked at 1 month ([2839.7 ± 101.4] µg/L), and decreased to the baseline ([370.3 ± 260.2] µg/L) 3 months after surgery. No death occurred, but 25 (10%) patients suffered recurrent angina in the one-year follow-up. They had significantly higher D-dimer level at one month after OPCAB than those of patients who did not suffer from angina. Preoperative ejection fraction <50% and D-dimer level >2915 µg/L at one month after surgery were significantly associated the recurrent angina.After OPCAB, patients have a higher level of D-dimer. And this lasts for a long period (about 3 months). It may reflect a certain degree of hypercoagulable and hyperfibrinolytic state after OPCAB.

Effects of microRNA-330 on vulnerable atherosclerotic plaques formation and vascular endothelial cell proliferation through the WNT signaling pathway in acute coronary syndrome.

This study is designed to investigate the effects of microRNA (miR)-330 on atherosclerotic plaques formation and vascular endothelial (VE) cell proliferation by targeting MAPK8 through the WNT signaling pathway in rats with acute coronary syndrome (ACS). Expression of hemodynamic variables were tested. Rats were allocated into control, blank, negative control (NC), miR-330 mimic, miR-330 inhibitor, DDK-1, miR-330 inhibitor + DDK-1 groups. ELISA was used to evaluate the expression of TC, TG, LDL-C, hs-CRP, IL-6, IL-10, TNF-α, and SAA. Immunohistochemistry, reverse transcription quantitative polymerase chain reaction and Western blotting were used for expression of VEGF, MAPK8, WNT1, ß-catenin, GSK-3ß, p-GSK-3ß, CyclinD1, MMP-9, IL-6, and IL-8. MTT assay and flow cytometry for cell proliferation and apoptosis. Compared with the control group, other groups had lower levels of SBP, DBP, MBP, LVSP, and miR-330, higher levels of HR, LVEDP, TC, TG, LDC-C, hs-CRP, IL-6, IL-10, TNF-α, SAA, higher positive protein expression rates of MAPK8, VEGF, and MMP-9, elevated WNT1, ß-catenin, GSK-3ß and CyclinD1, and reduced cell proliferation. MAPK8-3'-UTR was targeted by miR-330. Compared with the blank group, the miR-330 mimic and DDK-1 groups had higher levels of SBP, DBP, MBP, LVSP, lower levels of HR, LVEDP, TC, TG, LDC-C, hs-CRP, IL-6, TNF-α, SAA, elevated IL-10, decreased positive protein expression rates of MAPK8 and VEGF, raised cell proliferation and reduced cell apoptosis rates. We conclude that overexpressed miR-330 suppresses atherosclerotic plaques formation while promotes VE cell proliferation by targeting MAPK8 through the WNT signaling pathway in ACS rats.

[Effect of D-dimer and tissue factor-1208D/I gene polymorphism on the prognosis of patients with off-pump coronary artery bypass grafting].

OBJECTIVE: To investigate the effect of perioperative period D-dimer and tissue factor (TF)-1208D/I gene polymorphism on the long-term prognosis of patients with off-pump coronary artery bypass grafting (OPCABG). METHODS: Retrospective analysis of the case data of the first OPCABG patients admitted to Tianjin Medical University General Hospital from May 2015 to May 2016 were enrolled. The general data, operation time, bypass number, left ventricular ejection fraction (LVEF), flow rate of 24-hour pleural effusion, intraoperative heparin dosage, combined anticoagulant and antiplatelet time, and the time of postoperative ventilator were measured. The blood biochemical indexes of 1, 4, 7, 14 days and 1, 2, 3 months after operation, perioperative complications, the level of D-dimer in the patients with different TF-1208D/I gene polymorphism, and prognosis of 1-year follow-up were recorded. The risk factors of recurrent angina 1 year after operation was analyzed by Logistic regression analysis. RESULTS: The level of plasma D-dimer was increased continuously after OPCABG, and reached a peak at 1 month after operation [1.94 (1.07, 2.70) mg/L], then decreased, and decreased to preoperative level 3 months after operation [0.20 (0.10, 0.45) mg/L]. The level of D-dimer in TF-1208II genotype was significantly higher than that in TF-1208DD genotype and TF-1208D/I genotype group at 14 days and 1 month after operation [mg/L: 4.17 (1.54, 5.09) vs. 1.91 (1.07, 2.26), 1.02 (0.91, 1.88) at 14 days; 5.12 (2.41, 6.32) vs. 1.94 (1.18, 2.70), 1.62 (0.22,1.88) at 1 month, all P < 0.05]. The results of 1-year follow-up showed that 25 patients with recurrent angina pectoris without the occurrence of myocardial infarction. The proportion of recurrent angina pectoris in TF-1208II genotype was significantly higher than that in TF-1208DD genotype and TF-1208D/I genotype group (χ2 = 0.197, P = 0.004). Logistic regression analysis showed that LVEF < 0.50 [odds ratio (OR) = 6.482, 95% confidence interval (95%CI) = 1.365-18.763, P = 0.015] and TF-1208II genotype (OR = 8.864, 95%CI = 1.613-46.743, P = 0.012) were independent risk factors for recurrent angina pectoris at 1 year after OPCABG. CONCLUSIONS: After OPCABG, the body was in a hypercoagulable state and lasted for a long time, and almost recovered 3 months after operation. LVEF < 0.50 and TF-1208 II genotype were independent risk factors of angina pectoris at 1 year after surgery.

Polymorphisms of VKORC1 and CYP2C9 are associated with warfarin sensitivity in Chinese population.

OBJECTIVE: Warfarin is a commonly prescribed anticoagulant for prevention of thromboembolic events. Wide inter-individual dose variation, narrow therapeutic range and risk of serious bleeding result in difficulties in achieving the therapeutic effect. The present study was designed to clarify the real biological significance of the polymorphisms of VKORC1 and cytochrome P450 2C9 (CYP2C9) in warfarin metabolism. METHODS: A total of 214 patients with warfarin anticoagulant therapy were selected. During follow-up of anticoagulation, warfarin dosage and associated international normalized ratio values were recorded. Genetic polymorphisms of VKORC1 promoter and from exon 1 to exon 3 and CYP2C9 exon 4 sequence were detected by polymerase chain reaction and gene sequencing. RESULTS: Five polymorphisms were identified in this research, which were VKORC1 1173C>T (intron 1), 1542G>C (intron 2), 2255C>T (intron 2), 3730C>T (3'-downstream) and CYP2C9 exon 4 -65G>C. VKORC1 1173CT, 1542GC, 2255CT and 3730CT polymorphisms were detected in same patients, but CYP2C9 exon 4 -65GC carriers were different from them. VKORC1 1173CT, 1542GC, 2255CT, 3730CT carriers and CYP2C9 exon 4 -65GC carriers had significantly higher warfarin daily dosage than others (3.2±0.6 vs 3.1±1.1 vs 2.6±0.8 mg/day). Logistic regression analysis revealed VKORC1 1173CT, 1542GC, 2255CT, 3730CT carrier status (odds ratio [OR] =3.233, 95% confidence interval [CI]: 1.259-8.303, P=0.015) and obesity with body mass index >27 kg/m2 (OR =1.223, 95% CI: 1.097-1.363, P<0.001) to have independent and statistically significant contributions to high warfarin dosage. CONCLUSION: In general, in VKORC1 1173CT, 1542GC, 2255CT and 3730CT carriers and in obese patients, warfarin maintenance doses were significantly higher than in the others.

miR-214 down-regulates ARL2 and suppresses growth and invasion of cervical cancer cells.

Increasing evidence has shown that miRNAs are implicated in carcinogenesis and can function as oncogenes or tumor suppressor genes in human cancers. In this study, we confirmed that miR-214 is frequently down-regulated in cervical cancer compared with normal cervical tissues. Ectopic expression of miR-214 suppressed proliferation, migration and invasion of HeLa and C33A cervical cancer cells. Bioinformatics analysis revealed that ADP ribosylation factor like 2 (ARL2) was a potential target of miR-214 and was remarkably up-regulated in cervical cancer. Knockdown of ARL2 markedly inhibited cervical cancer cell proliferation, migration and invasion, similarly to over-expression of miR-214, indicating that ARL2 may function as an oncogene in cervical cancer. In conclusion, our study revealed that miR-214 acts as a tumor suppressor via inhibiting proliferation, migration and invasion of cervical cancer cells through targeting ARL2, and that both miR-214 and ARL2 may serve as prognostic or therapeutic targets for cervical cancer.

Congenital Blaschkoid Angiolymphoid Hyperplasia With Eosinophilia of the Anogenital Region.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, idiopathic vascular disorder. It manifests as dermal or subcutaneous red to brown papules or nodules, most commonly on the head and neck; other less common sites include the trunk, extremities, genitalia, lips, and oral mucosa. Although ALHE is a benign disease, lesions are often persistent and difficult to eradicate. ALHE occurs more frequently in Asian young and middle-aged women. Histologically, it is characterized by a florid vascular proliferation with hobnail epithelioid endothelial cells surrounding by lymphocytic and eosinophilic infiltrate. Here, we reported congenital ALHE in a 2-year-old girl. Unilateral lesions had a blaschkoid segmental distribution in the anogenital region and were successfully treated with the Nd:YAG laser.

High Level of von Willebrand Factor in Non-ST Segment Elevation Myocardial Infarction Patients Predicted Cardiovascular Ischemic Events After Off-Pump Coronary Artery Bypass Surgery.

The aim of our study was to determine the characteristics and value of plasma von Willebrand factor antigen (vWF: Ag) levels after off-pump coronary artery bypass grafting (OPCAB) surgery in predicting the risk of cardiovascular ischemic events.A retrospective cohort analysis of 203 non-ST-segment elevation myocardial infarction patients was performed. Patients were divided into a poor recovery group and a stable condition group according to whether ischemic events occurred or not within 90 days postoperatively. The level of vWF: Ag was detected using a blood coagulation analyzer. SPSS17.0 statistical software was used for data analysis. The Friedman rank sum test and Mann-Whitney U test were used for intra-group and inter-group data analysis, respectively. The diagnostic performance of vWF: Ag was evaluated by receiver operating characteristic (ROC) curve analysis.Plasma vWF: Ag levels at postoperative days 14, 30, 60, and 90 in the poor recovery group were significantly higher than those at the corresponding time points in the stable group. The area under the ROC curve in diagnosing adverse events was 0.927 (95% CI: 0.867~0.987) with 96.6% sensitivity and 58.6% specificity when the cut-off value of vWF: Ag was 233% at postoperative day 30.The changing characteristics of plasma vWF: Ag sensitively reflect the degree of vascular endothelial injury of OP-CAB patients and might serve as a surrogate marker of the adverse event of non-ST segment elevation myocardial infarction.

Estimation of venous thromboembolism risk with thrombotic biomarkers in cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the value of thrombotic biomarkers in estimation of venous thromboembolism (VTE) risk in cancer patients.</p><p><b>METHODS</b>A total of 1473 cancer patients treated in the Tianjin Medical University General Hospital from 2009 to 201 were selected, including 845 males and 628 females in the age of 56 ± 17 years. The activities of von Willebrand factor antigen (vWF:Ag), factor VII (F VII:A), factor VIII (F VIII:A), antithrombin (AT:A), protein C (PC:A) and protein S (PS:A) were assayed using an ACL TOP 700 blood coagulation analyzer. The level of D-dimer (D-D) was assayed using the Biomerieux Mini Vidas Automated Immunoassay Analyzer. Receiver operating characteristic curve (ROC) was used to analyze the diagnostic performance of the parameters. Cox regression analysis model was applied to evaluate the effect on prognosis, and Kaplan-Meier curve was used to implement the survival analysis.</p><p><b>RESULTS</b>The levels of vWF:Ag, D-D, and F VIII:A were significantly higher in all the specified tumor groups ( except the other tumor group ) than that of the control groups (P < 0.05). F VIII:A was significantly higher than that in the control group in all tumor groups except the renal carcinoma, prostatic cancer, lymphoma groups and the other tumor group (P < 0.05). The PC:A level was significantly lower in all tumor patients groups than in the control group, except glioma, breast cancer, gastric carcinoma, renal carcinoma and the other tumors groups (P < 0.05). The PS: A level was significantly lower in all tumor groups than in the control group, except the glioma, breast cancer, prostatic cancer, lymphoma and the other tumors groups (P<0.05). The AT: A level was significantly lower in all tumor groups than in the control group (P<0.05). When the optimum cut-off point of vWF:Ag for VTE diagnosis was 192% in the cancer group, the area under ROC curve = 0.828 (95% CI: 0.716 to 0.939). When the optimum cut-off point of D-dimer for VTE diagnosis was 1484 ng/ml in the cancer group, the area under ROC curve = 0.915 (95% confidence interval: 0. 840 to 0.988). When the optimum cut-off point of PC: A for VTE diagnosis was 75.2% in the cancer group, the area under ROC curve = 0.764 (95% confidence interval: 0.630 to 0.898). The Cox analysis showed that age, surgery, chemotherapy and D-dimer were independent risk factors for VTE event within three months in cancer patients. The cumulative probability of VTE was increased significantly in the cancer patients if whose plasma D-dimer level was over the cut-off value.</p><p><b>CONCLUSIONS</b>The plasma D-dimer level is obviously increased in cancer patients, and there is a relevance to thrombosis risk stratification and VTE cumulative probability. It is with good diagnostic performance, and may be used as an effective marker in estimation of VTE risk within 3 months in cancer patients.</p>

Polymorphisms and high on-aspirin platelet reactivity after off-pump coronary artery bypass grafting.

OBJECTIVES: High on-aspirin residual platelet reactivity (RPR) after coronary artery bypass grafting (CABG) is a transient phenomenon with important implications for graft patency. This study was designed to determine the role of polymorphisms [TBXA2R (T924C), GPIIIa (Pl(A1/A2)), P2Y1 (A1622G), and GP1Bα (C1018T)] on RPR in Chinese patients undergoing off-pump CABG (OPCAB). METHODS: Of 420 patients recruited to this study, 210 patients underwent primary OPCAB and 210 controls with ischemic heart disease received optimal medical therapy. Arachidonic acid-induced platelet aggregation and urinary 11-dehydro thromboxane B2 were measured at baseline and following aspirin administration on days 1, 4, 10, and on 6th month. Four polymorphisms were identified [TBXA2R (T924C), P2Y1 (A1622G), Pl(A1/A2) and GP1Bα (C1018T)]. RESULTS: On the first post-operative day, 62 patients (29.5%) were with high RPR and 148 (70.5%) were with low RPR. Of the former, 33 (15.7%), 10 (4.6%), and 0 (0%) patients remained with high RPR on days 4, 10, and on 6 month, respectively. No individuals with high RPR was found in controls. Logistic regression identified TBXA2R-924TT (OR = 4.5; 95% CI, 1.8-11.1) and body mass index > 27 kg/m(2) (OR = 2.73; 95% CI, 1.1-7.0) as independent risk factors for high on-aspirin RPR. CONCLUSIONS: High on-aspirin RPR after OPCAB is associated with genetic polymorphism TBXA2R-924TT and obesity.

Aspirin resistance in off-pump coronary artery bypass grafting.

OBJECTIVE: Anti-platelet therapy with aspirin is the cornerstone of treatment after coronary artery bypass grafting (CABG). Aspirin resistance describes the clinical observation of the inability of aspirin to prevent thrombotic complications or the laboratory phenomenon of absence of the effect of aspirin on platelet inhibition tests. Off-pump CABG (OPCAB) is associated with reduced platelet activation and turnover compared to on-pump surgery which may indicate that aspirin is more effective after OPCAB. Our aim was to evaluate the efficacy of aspirin and incidence of aspirin resistance in patients undergoing OPCAB. METHODS: A total of 331 patients was recruited, of which 111 underwent primary OPCAB (group A) and 220 controls with ischaemic heart disease received medical therapy. Arachidonic acid-induced platelet aggregation and urinary 11-dehydro thromboxane B2 (11-dehydroTxB2) were measured at baseline and following aspirin administration on days 1, 4 and 10. A 6-month follow-up was completed in patients who developed aspirin resistance. RESULTS: On the first postoperative day, 78 patients (70.3%) were aspirin sensitive (AS) and 33 (29.7%) were aspirin resistant (AR). Of the latter, 18 (16.2%) and five (4.5%) patients remained resistant on days 4 and 10, respectively. AR patients had significantly greater platelet aggregation and urinary 11-dehydroTxB2 levels at all time points than those in the AS group. All patients in the AR group were AS by 6 months. All controls were sensitive to aspirin with similar platelet aggregation and 11-dehydroTxB2 to those in the AS group. CONCLUSIONS: Aspirin resistance is a transient phenomenon during the early postoperative period in approximately 30% of patients undergoing OPCAB.

Effect of polymorphism and type II diabetes on aspirin resistance in patients with unstable coronary artery disease.

BACKGROUND: Aspirin is widely used in the secondary prevention of coronary artery diseases, including myocardial infarction, stroke, and vascular related deaths. However, the antiplatelet effect of aspirin appears to be variable and aspirin resistance (AR) is currently still controversial for Chinese patients. The aim of this study was to describe the prevalence of AR, and identify possible risk factors associated with a lack of response to aspirin treatments in patients with unstable coronary artery disease. METHODS: Platelet function tests with arachidonic acid (ARA) and urinary 11-dehydro-thromboxane B2 (11-DH-TXB2) concentrations were performed in 262 patients with unstable coronary artery disease who had not been taking aspirin before admission. ARA induced platelet aggregation and 11-DH-TXB2 were detected to evaluate the functional and biochemical responses to aspirin before and on days 1, 4, and 10 after aspirin administration. Six-month follow-up was completed in patients who developed AR to evaluate the effect of aspirin in a long-term treatment. GP1Bα (C1018T), Pl (A1/A2), P2Y1 (A1622G), TBXA2R (T924C) were also detected to evaluate the influence of genetic variant on aspirin responsiveness. RESULTS: A total of 8.8% of patients were indentified as AR at the first day after aspirin treatment. The level of urine 11-DH-TXB2 in the AR group was higher compared to non-AR group (P < 0.05). There was no relationship between ARA induced platelet aggregation and urinary 11-DH-TXB2 levels (r = 0.038, P = 0.412). The results of DNA sequencing showed that TBXA2R-924TT homozygotes had a significantly high rate of AR. Logistic regression demonstrated that diabetes was an independent risk factor of AR. CONCLUSIONS: In the beginning period of administration, aspirin was not a sufficient factor that inhibits platelet aggregation. TBXA2R-924T allele was involved in AR. Diabetes was an independent risk factor of AR.

[Application of wavelet transform on improving detecting precision of the non-invasive blood components measurement based on dynamic spectrum method].

Time-varying noises in spectra collection process have influence on the prediction accuracy of quantitative calibration in the non-invasive blood components measurement which is based on dynamic spectrum (DS) method. By wavelet transform, we focused on the absorbance wave of fingertip transmission spectrum in pulse frequency band. Then we increased the signal to noise ratio of DS data, and improved the detecting precision of quantitative calibration. After carrying out spectrum data continuous acquisition of the same subject for 10 times, we used wavelet transform de-noising to increase the average correlation coefficient of DS data from 0.979 6 to 0.990 3. BP neural network was used to establish the calibration model of subjects' blood components concentration values against dynamic spectrum data of 110 volunteers. After wavelet transform de-noising, the correlation coefficient of prediction set increased from 0.677 4 to 0.846 8, and the average relative error was decreased from 15.8% to 5.3%. Experimental results showed that the introduction of wavelet transform can effectively remove the noise in DS data, improve the detecting precision, and accelerate the development of non-invasive blood components measurement based on DS method.

[Association of polymorphisms of cytochrome P450 2C9 exon 4 and -65G>C with warfarin sensitivity].

OBJECTIVE: To investigate the association of the polymorphisms of cytochrome P450 2C9 (CYP2C9) exon 4 608T/G, 561A/C, 537A/C and 527A/C, and -65G/C with warfarin sensitivity. METHODS: A total of 102 patients under warfarin anticoagulant therapy were selected. During follow-up, warfarin dosage and associated Prothrombin Time-International Normalized Ratio (P-INR) values were recorded. Simultaneous monitoring of incidence of bleeding and thrombosis adverse effect was recommended. Genetic polymorphisms of the above mentioned loci were identified by polymerase chain reaction and DNA sequencing. RESULTS: The average age of the 102 patients was (62.1+/-10.5) years. The body mass index (BMI) was (24.7+/-3.8) kg/m2. Mean daily warfarin requirement was from 1.250 to 5.077 mg/day when therapeutic PT-INR (1.5-2.5) was maintained. DNA sequencing showed no polymorphisms of 608T/G, 561A/C, 537A/C, 527A/C in CYP2C9 exon 4. Warfarin daily dosage in CYP2C9 exon 4 -65C carriers was 3.106+/-0.619 mg/d, while it was (2.555+/-0.708) mg/d in individuals with wild-type -65G (P=0.020). Receiver operating characteristic (ROC) analysis showed that warfarin daily dosage of more than 2.5 mg/d can be used to predict the CYP2C9 exon 4 -65GC genotype (AUC: 0.770, P=0.005, 95%CI:0.626-0.915). Logistic regression indicated that BMI was an independent factor of bleeding during anti-coagulation therapy (OR=0.794, 95%CI: 0.651-0.970, P=0.024). CONCLUSION: The Chinese population are, generally, warfarin-sensitive. Exon 4 of the CYP2C9 gene is highly conserved in this population. The warfarin maintenance dosage in CYP2C9 exon 4 -65CG carriers was significantly higher than those with wild-type -65GG. The clinical significance needs further investigation with more large-scale, multi-center trials.