Association between serum osteocalcin level and visceral obesity in Chinese postmenopausal women.

BACKGROUND: A low serum osteocalcin level, visceral obesity and postmenopausal status are recognized risk factors for cardiovascular disease. OBJECTIVE: We investigated the relationship between the serum osteocalcin level and visceral fat content in a population of Chinese postmenopausal women. DESIGN AND PATIENTS: In total, 1481 postmenopausal women (mean age ± standard deviation, 57·1 ± 4·8 years) were selected from the Shanghai Obesity Study. MEASUREMENTS: Abdominal fat accumulation was quantified using magnetic resonance imaging. Subjects with a visceral fat area (VFA) of ≥80 cm(2) were classified as abdominally obese. The total serum osteocalcin level was measured by electrochemiluminescence immunoassay. RESULTS: The median serum osteocalcin level was 20·66 µg/l (interquartile range, 16·88-25·42 µg/l). The overall prevalence of abdominal obesity was 49·1% (n = 727). Abdominally obese subjects had lower serum osteocalcin levels than did nonabdominally obese subjects [19·14 (16·02-23·82) vs 21·97 (18·14-26·77) µg/l, respectively; P < 0·001]. Partial correlation analysis showed that the serum osteocalcin level was still negatively correlated with VFA after adjusting for age, years since menopause and body mass index (P < 0·01). Moreover, VFA was independently associated with the serum osteocalcin level after adjustment for confounding factors (P < 0·05). A low serum osteocalcin level was an independent risk factor for abdominal obesity (odds ratio, 0·972; 95% confidence interval, 0·953-0·991; P = 0·004). CONCLUSION: The serum osteocalcin level was inversely correlated with the visceral fat content in these Chinese postmenopausal women.

Glycated albumin is more closely correlated with coronary artery disease than 1,5-anhydroglucitol and glycated hemoglobin A1c.

BACKGROUND: The aim of this study was to investigate the associations of two nontraditional glycemic markers, glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG), as well as glycated hemoglobin A1c (HbA1c) with coronary artery disease (CAD). METHODS: In total, 272 subjects (178 men and 94 postmenopausal women) were enrolled in this study. All of them underwent coronary angiography which was used to diagnose CAD. The severity of coronary artery stenosis was assessed by the coronary stenosis index (CSI). GA and 1,5-AG were assayed using the enzymatic method, and HbA1c was detected by high-pressure liquid chromatography. RESULTS: The HbA1c and GA levels were significantly higher in CAD group than those in non-CAD group (both P < 0.01). While the 1,5-AG level was significantly lower in CAD group than that in non-CAD group (P < 0.05). After adjustment for traditional risk factors of CAD, HbA1c, 1,5-AG, and GA, multivariate logistic regression analysis showed that GA was an independent risk factor for CAD (odds ratio = 1.143, 95% confidence interval: 1.048-1.247, P = 0.002). With CSI as a dependent variable, multiple stepwise regression analysis demonstrated an independent positive correlation between GA and CSI (standardized ß = 0.184, P = 0.003), beyond gender, age, and lipid-lowering therapy, after adjustment for traditional risk factors of CAD, HbA1c, 1,5-AG, and GA. CONCLUSIONS: GA was more closely correlated with CAD than HbA1c and 1,5-AG in a Chinese population with high risk of CAD.

Relationship between serum osteocalcin level and carotid intima-media thickness in a metabolically healthy Chinese population.

BACKGROUND: The relationship between osteocalcin and atherosclerosis remains unclear. This might be due to different degrees of confounding from factors that are associated with serum osteocalcin level, such as metabolic-related variables. This study aimed to investigate the relationship between serum osteocalcin level and carotid intima-media thickness (C-IMT) in a metabolically healthy population. METHODS: A total of 476 subjects with normal values for weight, glucose tolerance, blood pressure, and lipids (age range, 20-75 years; 155 men, 201 premenopausal women, 120 postmenopausal women) from the Shanghai Obesity Study were recruited for this cross-sectional study. Subjects with a history of cardiovascular disease or carotid plaque were excluded. C-IMT was measured by ultrasonography. Serum osteocalcin level was assessed by an electrochemiluminescence immunoassay. RESULTS: Median C-IMT in the entire study population was 0.55 mm with an interquartile range of 0.50-0.60 mm. C-IMT in premenopausal women was significantly lower than that in men and postmenopausal women (all P < 0.001). The median (interquartile range) of serum osteocalcin level in the entire population was 17.02 (13.31-21.47) ng/mL. Serum osteocalcin level in postmenopausal women was significantly higher than that in men and premenopausal women (all P < 0.001), while the level of serum osteocalcin in men was also significantly higher than that in premenopausal women (P < 0.001). No significant correlation was found between C-IMT and serum osteocalcin level in either men or postmenopausal women. There was a significant, inverse correlations between C-IMT and serum osteocalcin level in premenopausal women after adjustment of age, but this association was eliminated after adjustment for other confounding factors. CONCLUSIONS: Serum osteocalcin level was not independently associated with C-IMT in a metabolically healthy Chinese population.

Inverse relationship between serum osteocalcin levels and nonalcoholic fatty liver disease in postmenopausal Chinese women with normal blood glucose levels.

AIM: Osteocalcin is involved in the progression of nonalcoholic fatty liver disease (NAFLD) in animal models and humans. In this study we investigated the relationship between serum osteocalcin levels and NAFLD in postmenopausal Chinese women. METHODS: A total of 733 postmenopausal women (age range: 41-78 years) with normal blood glucose levels were enrolled in this cross-sectional study. Women taking lipid-lowering or anti-hypertensive drugs were excluded. Serum osteocalcin levels were assessed using an electrochemiluminescence immunoassay. The degree of NAFLD progression for each subject was assessed through ultrasonography. The fatty liver index (FLI) of each subject was calculated to quantify the degree of liver steatosis. RESULTS: The median level of serum osteocalcin for all subjects enrolled was 21.99 ng/mL (interquartile range: 17.84-26.55 ng/mL). Subjects with NAFLD had significantly lower serum osteocalcin levels (18.39 ng/mL; range: 16.03-23.64 ng/mL) compared with those without NAFLD (22.31 ng/mL; range: 18.55-27.06 ng/mL; P<0.01). Serum osteocalcin levels decreased with incremental changes in the FLI value divided by the quartile (P-value for trend<0.01). The serum osteocalcin levels showed a negative correlation with the FLI values, even after adjusting for confounding factors (standardized ß=-0.124; P<0.01). Binary logistic regression analysis identified an individual's serum osteocalcin level as an independent risk factor for NAFLD (odds ratio: 0.951; 95% confidence interval: 0.911-0.992; P=0.02). CONCLUSION: Serum osteocalcin levels are inversely correlated with NAFLD in postmenopausal Chinese women with normal blood glucose levels.

Serum vitamin D levels are inversely related with non-alcoholic fatty liver disease independent of visceral obesity in Chinese postmenopausal women.

The aim of the present study was to investigate the association between serum vitamin D levels and both visceral adipose and with non-alcoholic fatty liver disease (NAFLD) in Chinese postmenopausal women. Four hundred and fifty-one postmenopausal women between 45 and 74 years of age (mean (± SD) age 57.3 ± 4.6 years) were enrolled in the study. All subjects participated in the Shanghai Obesity Study between June and August 2011 and underwent abdominal magnetic resonance imaging and an abdominal ultrasonography. Patients with a visceral fat area (VFA) ≥ 80 cm(2) were classified as abdominally obese. Serum 25-hydroxyvitamin D3 (25(OH)D3 ) levels were measured with an electrochemiluminescence immunoassay. The prevalence of NAFLD in the study population was 34.8% (n = 157). Women with abdominal obesity had significantly lower serum 25(OH)D3 levels than those without abdominal obesity (median (interquartile range) 11.23 (8.64-14.12) vs 12.56 (9.41-15.98) ng/mL, respectively; P < 0.01). Regardless of abdominal obesity status, serum 25(OH)D3 levels in patients with NAFLD were lower than those without non-NAFLD (11.14 (8.63-13.81) vs 12.92 (9.48-16.37) ng/mL (P < 0.05) for those without abdominal obesity; 10.86 (8.61-13.56) vs 11.55 (8.82-16.38) ng/mL (P < 0.05) for those with abdominal obesity). Partial correlation analyses demonstrated a negative correlation between serum 25(OH)D3 levels and VFA (P < 0.05). Logistic regression analysis revealed that high serum 25(OH)D3 levels were a protective factor against NAFLD after adjusting for risk factors such as VFA. In conclusion, independent of visceral obesity, vitamin D is inversely correlated with NAFLD in Chinese postmenopausal women.

Fibroblast growth factor 23 is associated with the presence of coronary artery disease and the number of stenotic vessels.

Fibroblast growth factor 23 (FGF23) has been reported to be involved in cardiovascular disease. The aim of this study was to investigate the association between FGF23 and the presence of coronary artery disease (CAD), as well as the number of stenotic vessels. A total of 254 eligible participants (167 men and 87 postmenopausal women) were enrolled in this study. Coronary angiography was used for diagnosis of CAD. Serum intact FGF23 levels were determined by a two-sided sandwich enzyme-linked immunosorbent assay. The median serum FGF23 levels of the entire study population were 39.9 (33.1-47.5) pg/mL. Serum FGF23 levels were higher in subjects with one-vessel disease than those without CAD (P < 0.05), which further increased significantly in the subjects with multi-vessel disease (P < 0.05). Serum FGF23 levels increased with cumulative number of stenotic vessels (P for trend < 0.001). Multiple stepwise regression analysis revealed estimated glomerular filtration rate (standardized ß = -0.298; P < 0.001) and body mass index (standardized ß = 0.132; P = 0.049) were independent factors correlated with FGF23. Multivariate logistic regression analysis showed that FGF23 was positively and independently associated with the presence of CAD (odds ratio = 1.058, 95% confidence interval = 1.025-1.092; P = 0.001). Additionally, FGF23 was also correlated with multi-vessel disease significantly (odds ratio = 1.034, 95% confidence interval = 1.007-1.062; P = 0.013). In conclusion, serum FGF23 levels exhibit positive and independent association with the presence of CAD and increase with the cumulative number of stenotic vessels.

Associations of glycated haemoglobin A1c and glycated albumin with subclinical atherosclerosis in middle-aged and elderly Chinese population with impaired glucose regulation.

The aim of this study was to investigate the correlations of glycated haemoglobin A1c (HbA1c) and glycated albumin (GA) with subclinical atherosclerosis in middle-aged and elderly Chinese populations with impaired glucose regulation (IGR). In total, 640 subjects with IGR and no history of cardiovascular disease or carotid artery plaque were recruited for this study (256 men, 384 women; age range, 40-70 years). The carotid intima-media thickness (C-IMT) measured by carotid ultrasonography was used as an indicator of subclinical atherosclerosis. Increased C-IMT was defined as ≥ 0.70 mm (upper quartile). HbA1c and GA were measured with high-performance liquid chromatography and enzymatic method, respectively. The average HbA1c and GA among all 640 subjects were 5.7 ± 0.3% and 14.0 ± 1.1%, respectively. HbA1c and GA were higher in subjects with increased C-IMT than in subjects with normal C-IMT (5.8 ± 0.3% vs 5.7 ± 0.3% and 14.2 ± 1.0% vs 13.9 ± 1.1%, respectively; both P < 0.01). Correlation analysis showed that both HbA1c and GA were positively correlated with C-IMT (r = 0.135 and 0.112, respectively; both P < 0.01). Logistic regression analysis revealed that both HbA1c (odds ratio (OR), 2.630; 95% confidence interval (95% CI), 1.401-4.935; P = 0.003) and GA OR, 1.215; 95% CI, 1.008-1.466; P = 0.041) were independent risk factors for increased C-IMT. Both HbA1c and GA reflect the risk of subclinical atherosclerosis in middle-aged and elderly Chinese populations with IGR.

Serum vitamin D is associated with non-alcoholic fatty liver disease in Chinese males with normal weight and liver enzymes.

AIM: Considering the characterization of vitamin D deficiency as a risk factor of ectopic fat deposition, the association of serum 25-hydroxy vitamin D3 [25(OH)D3] levels with non-alcoholic fatty liver disease (NAFLD) was evaluated in Chinese men with normal body mass index (BMI) and enzyme markers of liver function. METHODS: A total of 514 participants (22 to 79 years old) with normal BMI and liver enzymes were identified for analysis. Abdominal ultrasound was performed to diagnose NAFLD, and the fatty liver index (FLI) was calculated to quantify liver steatosis. Serum 25(OH)D3 levels were determined by an electrochemiluminescence immunoassay. RESULTS: Among the entire study population, the mean levels of serum 25(OH)D3 were 15.32±5.77 ng/mL. However, when serum 25(OH)D3 levels were compared between non-NAFLD subjects (n=438) and NAFLD subjects (n=76), the latter showed significantly lower levels (15.65±5.89 ng/mL vs 13.46±4.65 ng/mL, P=0.002). In addition, serum 25(OH)D3 levels were found to be significantly correlated with FLI after adjustment for age and BMI (r=-0.108, P=0.014). Logistic regression showed that serum 25(OH)D3 levels were independently correlated with NAFLD (OR: 0.937, 95% CI: 0.884-0.993, P=0.028). Furthermore, stepwise regression analysis revealed that serum 25(OH)D3 levels were inversely associated with FLI (ß=-0.055, P=0.040). CONCLUSION: The present study demonstrated that serum 25(OH)D3 levels were inversely associated with NAFLD, even in subjects with normal total body fat, suggesting a potential role of lower levels of vitamin D in the occurrence and development of NAFLD.

Additional role of serum 25-hydroxyvitamin D3 levels in atherosclerosis in Chinese middle-aged and elderly men.

1. Perturbed serum vitamin D levels have been shown to be associated with increased risk of cardiovascular disease. The aim of the present study was to investigate the association of serum 25-hydroxyvitamin D3 (25(OH)D3) levels and B ultrasonography-detected carotid plaque and carotid intima-media thickness (C-IMT) in Chinese middle-aged and elderly men. 2. In all, 1001 men, aged 45-78 years, were enrolled in the study. Increased C-IMT was defined as any C-IMT value in the highest quartile of the study subjects (≥ 0.75 mm). 3. The study population had a median serum 25(OH)D3 level of 14.51 ng/mL (interquartile range (IQR) 10.84-18.67 ng/mL). Subjects with carotid plaques had lower serum 25(OH)D3 levels than those without (13.80 (IQR 10.82-17.68) vs 14.74 (IQR 10.87-19.08) ng/mL, respectively; P = 0.029), and decreasing serum 25(OH)D3 levels were accompanied by increased C-IMT in both groups (13.24 (IQR 9.91-16.81) vs 14.45 (IQR 11.40-18.51) ng/mL, respectively (P < 0.05) in those with plaque; 13.80 (IQR 9.99-17.09) vs 14.99 (IQR 11.17-19.43) ng/mL, respectively (P < 0.01) in those without plaque). Multivariate logistic regression analysis showed that serum 25(OH)D3 levels were independently associated with carotid plaque (odds ratio (OR) 0.972; 95% confidence interval (CI) 0.946-0.998; P = 0.032). In addition, serum 25(OH)D3 levels were identified as an independent protective factor for increased C-IMT among subjects with plaque (OR 0.900; 95% CI 0.849-0.955; P = 0.001) and those without plaque (OR 0.944; 95% CI 0.908-0.981; P = 0.004). 4. Collectively, these findings suggest that serum 25(OH)D3 levels are inversely associated with atherosclerosis in Chinese middle-aged and elderly men.

Additive relationship between serum fibroblast growth factor 21 level and coronary artery disease.

BACKGROUND: Expression and activity of the fibroblast growth factor (FGF) 21 hormone-like protein are associated with development of several metabolic disorders. This study was designed to investigate whether serum FGF21 level was also associated with the metabolic syndrome-related cardiovascular disease, atherosclerosis, and its clinical features in a Chinese cohort. METHODS: Two-hundred-and-fifty-three subjects visiting the Cardiology Department (Sixth People's Hospital affiliated to Shanghai JiaoTong University) were examined by coronary arteriography (to diagnose coronary artery disease (CAD)) and hepatic ultrasonography (to diagnose non-alcoholic fatty liver disease (NAFLD)). Serum FGF21 level was measured by enzyme-linked immunosorbent assay and analyzed for correlation to subject and clinical characteristics. The independent factors of CAD were determined by multivariate logistic regression analysis. RESULTS: Subjects with NAFLD showed significantly higher serum FGF21 than those without NAFLD (388.0 pg/mL (253.0-655.4) vs. 273.3 pg/mL (164.9-383.7), P < 0.01). Subjects with CAD showed significantly higher serum FGF21, regardless of NAFLD diagnosis (P < 0.05). Serum FGF21 level significantly elevated with the increasing number of metabolic disorders (P for trend < 0.01). After adjustment of age, sex, and BMI, FGF21 was positively correlated with total cholesterol (P < 0.05) and triglyceride (P < 0.01). FGF21 was identified as an independent factor of CAD (odds ratio = 2.984, 95% confidence interval: 1.014-8.786, P < 0.05). CONCLUSIONS: Increased level of serum FGF21 is associated with NAFLD, metabolic disorders and CAD.

Serum lipocalin-2 levels positively correlate with coronary artery disease and metabolic syndrome.

BACKGROUND: The lipocalin-2 (LCN2) cytokine, primarily known as a protein of the granules of human neutrophils, has been recently reported to be implicated in metabolic and inflammatory disorders. This study was designed to evaluate the relationship between serum LCN2 levels and coronary artery disease (CAD). METHODS: Serum LCN2 levels of 261 in-patients who underwent coronary angiography were measured by sandwich enzyme immunoassay. Demographic (169 men and 92 postmenopausal women) and clinical (metabolic syndrome (MS), triglyceride (TG) and C-reactive protein (CRP) levels) characteristics were collected to assess independent factors of CAD (CAD: 188 and non-CAD: 73) and serum LCN2 levels by multiple logistic regression and multivariate stepwise regression analyses, respectively. RESULTS: Serum LCN2 levels were significantly higher in men (37.5 (27.4-55.4) vs. women: 28.2 (18.7-45.9) ng/mL, p < 0.01) and men with CAD (39.2 (29.3-56.5) vs. non-CAD men: 32.7 (20.5-49.7) ng/mL, p < 0.05), and showed significant positive correlation with CAD in men (odds ratio = 2.218, 95% confidence interval: 1.017-4.839). Similarly, serum LCN2 levels were significantly higher in men with MS (40.2 (31.9-59.4) vs. non-MS: 32.0 (21.7-47.6) ng/mL, p < 0.01) and showed a significant positive correlation with the number of MS components (p for trend < 0.05). No significant differences or correlations were seen in women. TG and neutrophils (standard ß = 0.238 and 0.173) were independent factors of serum LCN2 levels in men, and only neutrophils (standard ß = 0.286) affected levels in women (all p < 0.05). CONCLUSIONS: Increased serum LCN2 levels are positively correlated with the presence of CAD and MS in a Chinese cohort.

Relationship between serum osteocalcin levels and non-alcoholic fatty liver disease in Chinese men.

The present study was designed to investigate the relationship between serum osteocalcin levels and non-alcoholic fatty liver disease (NAFLD) in Chinese men. In all, 1558 men (21-78 years old) were recruited to the study. Serum osteocalcin, glucose and lipid profiles were determined. Demographic and clinical characteristics were recorded. All participants underwent hepatic ultrasonographic examination. Serum osteocalcin levels were significantly lower in subjects with NAFLD than those without (P < 0.01). All study subjects were divided into four subgroups according to quartiles of serum osteocalcin levels. The frequency of NAFLD increased progressively with declining serum osteocalcin levels (P(trend) < 0.01). Serum osteocalcin levels were inversely correlated with NAFLD (P < 0.01). However, the significant association between serum osteocalcin levels and NAFLD disappeared in logistic regression analyses. Furthermore, multiple stepwise regression analysis showed that serum osteocalcin levels were independently associated with serum alanine aminotransferase levels in Chinese men (P < 0.01). The findings of the present study suggest that serum osteocalcin levels are not directly correlated with NAFLD.

[Changes in plasma levels of atrial natriuretic peptide, endothelin-1 and von Willebrand factor among newborns with persistent pulmonary hypertension].

OBJECTIVE: To investigate the changes in plasma levels of atrial natriuretic peptide (ANP), endothelin-1 (ET-1) and von Willebrand factor (vWF), and their significance among newborns with persistent pulmonary hypertension (PPH). METHODS: Sixty-six newborns with PPH (case group) (mild: 26 cases; moderate: 21 cases; severe: 19 cases), as well as 40 newborns without PPH (control group) who were hospitalized in the same period, were enrolled. The control group underwent echocardiography on admission. The case group underwent echocardiography before treatment (with refractory hypoxemia) and after 7 days of treatment for measurement of pulmonary artery systolic pressure (PASP). Meanwhile, plasma levels of ANP, ET-1 and vWF were measured using ELISA. RESULTS: Before treatment, the case group had significantly higher plasma levels of ANP, ET-1 and vWF than the control group (P<0.05), and these indices increased as PASP rose. After 7 days of treatment, the children with mild or moderate PPH showed normal PASP, and their plasma levels of ANP, ET-1 and vWF were not significantly different from those of control group. The children with severe PPH had significant decreases in all indices, but they were significantly higher than those of the control group. Plasma levels of ANP, ET-1 and vWF were significantly positively correlated with PASP before and after treatment (P<0.01). CONCLUSIONS: Changes in plasma levels of ANP, ET-1 and vWF can reflect PASP in newborns with PPH during treatment. Dynamic monitoring of these indices can help to judge the severity of PPH and guide treatment.

[Associations of glycated albumin level with coronary artery disease].

OBJECTIVE: To explore the associations of the level of glycated albumin (GA) with coronary artery disease (CAD). METHODS: A total of 306 patients undergoing coronary angiography (CA) were collected. There were 201 males and 105 females with an age range of 38-86 years. CA was the major diagnostic criteria of CAD. Metabolic syndrome was diagnosed according to the Guideline on Prevention & Treatment of Blood Lipid Abnormality in Chinese Adults. RESULTS: (1) CAD was found in 227 patients (74.2%). The levels of 2 h postprandial glucose, GA and hemoglobin A1c in the CAD patients were higher than those in the non-CAD counterparts (all P < 0.05). (2) In the subgroup of normal glucose tolerance (NGR), the CAD patients had a higher level of GA than the non-CAD patients ((15.0 ± 2.1)% vs (13.3 ± 1.7)%, P < 0.01). And the level of GA was higher in the patients with 1-vessel ((14.8 ± 2.1)% vs (13.3 ± 1.7)%, P < 0.05) and multi-vessel lesions ((15.1 ± 2.1)% vs (13.3 ± 1.7)%, P < 0.05) than that in the non-CAD counterparts (all P < 0.05). Similar results were obtained in the hyperglycemia subgroup. (3) Logistic regression demonstrated that the level of GA was independently correlated with CAD after adjusting other traditional factors among all subjects, NGR and hyperglycemia subgroup. CONCLUSIONS: The serum level of GA becomes significantly elevated the CAD patients. And it is an independent risk factor of CAD in both hyperglycemic and NGR patients.

COX-2 Forms Regulatory Loop with YAP to Promote Proliferation and Tumorigenesis of Hepatocellular Carcinoma Cells.

COX-2 and YAP are shown to be highly associated with hepatocellular carcinoma (HCC) and frequently upregulated during tumor formation. However, despite their importance, whether there is a mutual interaction between COX-2 and YAP and how they regulate each other are not clear. In this paper, we showed that COX-2 overexpression in HCC cell lines resulted in increased levels of YAP mRNA, protein, and its target genes. COX-2 promoted proliferation of HCC cell lines, and knockdown of YAP antagonized this effect. In addition, our results indicated that EP2 and Wnt/ß-Catenin mediate the transcriptional induction of YAP by COX-2. On the other hand, YAP increased COX-2 expression at the level of transcription requiring intact TEAD binding sites in the COX-2 promoter. Collectively, these findings indicated that COX-2 is not only a stimulus of YAP but also a target of Hippo-YAP pathway, thus forming a positive feedback circuit, COX-2-PGE2-EP2-Gαs-ß-catenin-YAP-COX-2. In a further study, we showed that inhibition of YAP and COX-2 acted synergistically and more efficiently reduced the growth of HCC cells and tumor formation than either of them alone, suggesting that dual governing of YAP and COX-2 may lead to the discovery of promising therapeutic strategies for HCC patients via blocking this positive feedback loop.

Successful treatment with rivaroxaban of cerebral venous thrombosis and bone marrow necrosis induced by pegaspargase: A case report and literature review.

RATIONALE: Pegaspargase has been used in the treatment of acute lymphoblastic leukemia with promising results. However, it has also been associated with several potentially serious complications, including thrombosis. Pegaspargase-induced cerebral venous thrombosis and bone marrow necrosis are very rare. PATIENT CONCERNS: A 50-year-old female developed headache, weakness of the right lower extremity, fever, and bone pain after chemotherapy including pegaspargase for the treatment of acute lymphoblastic leukemia. DIAGNOSES: Her imaging studies and bone marrow examinations were compatible with cerebral venous thrombosis and bone marrow necrosis. INTERVENTIONS: The patient received anticoagulation therapy with rivaroxaban. OUTCOMES: After treatment with rivaroxaban, she had a good outcome without major or minor bleeding. LESSONS: Clinicians should be aware of the very rare but possible induction of bone marrow necrosis during pegaspargase treatment when there is necrosis in other organs. Because of its greater safety and convenience, rivaroxaban gains popularity over traditional anticoagulant drugs.

YAP transcriptionally regulates COX-2 expression and GCCSysm-4 (G-4), a dual YAP/COX-2 inhibitor, overcomes drug resistance in colorectal cancer.

BACKGROUND: Chemotherapy resistance remains a major challenge in cancer treatment. COX-2 (cyclooxygenase 2) is involved in drug resistance and poor prognosis of many neoplastic diseases or cancers. However, investigations identifying new modulators of COX-2 pathway and searching for new chemicals targeting these valid resistant biomarkers are still greatly needed. METHODS: HCT15, HCT-116, HT-29, COLO205, FHC, IMCE, SW480 cell lines were used to detect the expression of YAP and COX-2. Site-directed mutagenesis, luciferase reporter analysis and ChIP assay were used to test whether YAP activated COX-2 transcription through interaction with TEAD binding sites in the promoter of COX-2. Cell line models exhibiting overexpression or knockdown of some genes were generated using transfection agents. Coimmunoprecipitation was used to detect protein mutual interaction. mRNA and protein levels were measured by qRT-PCR and western blot respectively. RESULTS: Here, we reported that both YAP and COX-2 were overexpressed in colorectal cancer cells. YAP increased COX-2 expression at the level of transcription requiring intact TEAD binding sites in the COX-2 promoter. YAP conferred drug resistance through COX-2 and its related effectors such as MCL, MDR, Survivin. GCCSysm-4 (G-4), a YAP and COX-2 inhibitor, effectively inhibited both YAP and COX-2 activation, induced apoptosis and decreased viability in Taxol-resistant cells. Inhibition of YAP and COX-2 acted synergistically and more efficiently reduced the resistance of CRC cells than either of them alone. CONCLUSIONS: Our data provide new mechanisms that YAP is a new upstream regulator of COX-2 pathway and plays an important role in conferring resistance in CRC cells. G-4, targeting YAP-COX-2, may be a novel valuable strategy to combat resistance in CRC.

Inverse association of serum vitamin D in relation to carotid intima-media thickness in Chinese postmenopausal women.

OBJECTIVE: This study aimed to investigate the relationship between serum vitamin D level and carotid intima-media thickness (C-IMT) in Chinese postmenopausal women. METHODS: Nine hundred and twenty six Chinese postmenopausal women without carotid artery plaque or history of cardiovascular disease were selected for analysis. Measurements of serum 25 hydroxyvitamin D3 (25(OH)D3) concentration and C-IMT were made by electrochemiluminescence immunoassay and B-mode ultrasound, respectively. Trend analysis was conducted according to tertiles of C-IMT. RESULTS: The median serum 25(OH)D3 level was 11.03 ng/mL, with an interquartile range of 8.22-14.70. A decreasing trend of serum 25(OH)D3 level was accompanied by increased C-IMT tertiles (P for trend = 0.001). Correlation analysis found an inverse relationship between serum 25(OH)D3 level and C-IMT (r = -0.113, P = 0.001). After adjustment for confounding factors, multiple regression analysis showed that serum 25(OH)D3 level independently and negatively associated with C-IMT (Standard ß = -0.112, P < 0.001). Moreover, the inverse correlation of serum 25(OH)D3 with C-IMT was also found in a subgroup of women with normal glucose tolerance, blood pressure and body mass index, and without undergoing lipid-lowering therapy (standard ß = -0.140, P = 0.018). CONCLUSIONS: Serum 25(OH)D3 level was inversely correlated with C-IMT in Chinese postmenopausal women.

Associations of serum adipocyte fatty acid binding protein with body composition and fat distribution in nondiabetic Chinese women.

CONTEXT: Previous studies have demonstrated evidence of a positive relationship between serum adipocyte fatty acid binding protein (A-FABP) and obesity. However, associations of A-FABP with body composition and ectopic fat accumulation remain unclear. OBJECTIVE: This study aimed to elucidate the effect of body composition, visceral fat area (VFA), and subcutaneous fat area (SFA) on serum A-FABP levels in a cohort of Chinese women without diabetes mellitus. DESIGN, SETTING, AND PARTICIPANTS: A total of 2108 women without diabetes (760 premenopausal and 1348 postmenopausal women; age, 20-78 y) selected from the Shanghai Obesity Study were enrolled. MAIN OUTCOME MEASURES: VFA and SFA were measured by magnetic resonance imaging, and body composition was determined by bioelectrical impedance analysis. A high VFA was defined as ≥ 80 cm(2). A high SFA was defined as that above the 75th percentile cutoff point of the menopause-specific population, respectively. RESULTS: Serum A-FABP levels were higher in postmenopausal than premenopausal women (P < .001). Both premenopausal and postmenopausal women with an isolated high VFA had higher A-FABP levels than did those with an isolated high SFA (P = .017 and .002, respectively). In both body mass index (BMI) groups (< 25 and ≥ 25 kg/m(2)), women with a high VFA had higher serum A-FABP levels regardless of their menopausal status. Multiple stepwise regression analysis showed that A-FABP was independently associated with fat mass (Standardized ß = 0.417 and 0.252 for premenopausal and postmenopausal status, respectively, both P < .001). Moreover, VFA was identified as an independent risk factor for A-FABP in postmenopausal women (Standardized ß = 0.114, P = .001). Application of the same regression analyses model to the two BMI groups produced similar results in both BMI categories. CONCLUSIONS: Serum A-FABP levels were associated with fat mass, and were also influenced by VFA after menopause in Chinese women without diabetes mellitus.

1,5-anhydroglucitol is associated with early-phase insulin secretion in chinese patients with newly diagnosed type 2 diabetes mellitus.

BACKGROUND: The goal of the present study was to explore the correlations of 1,5-anhydroglucitol (l,5-AG), glycated hemoglobin (HbA1c), and glycated albumin (GA) with insulin sensitivity and secretion. SUBJECTS AND METHODS: In total, 302 patients with newly diagnosed type 2 diabetes mellitus (166 men, 136 women) were enrolled in this study. The homeostasis model assessment for insulin resistance (HOMA-IR) and homeostasis model assessment for ß-cell function (HOMA-ß) were calculated to determine the basal insulin sensitivity and secretion. The insulinogenic index (IGI) was used to evaluate early-phase insulin secretion. 1,5-AG and GA were assayed via the enzymatic method, and HbA1c was detected by high-pressure liquid chromatography. RESULTS: Among all 302 subjects, the serum 1,5-AG level was 13.1±7.2 µg/mL, and the HbA1c and GA levels [median (interquartile range)] were 6.7% (6.2-7.3%) and 17.7% (16.0-19.5%), respectively. Increased 1,5-AG quartiles were accompanied by trends toward a decreased HOMA-IR and an increased HOMA-ß and IGI (for all trends, P<0.001). 1,5-AG was negatively associated with HOMA-IR (r=-0.200, P<0.001) and positively associated with HOMA-ß and IGI (r=0.210 and 0.413, respectively; both P<0.001). 1,5-AG was independently related to HOMA-IR and HOMA-ß and exhibited an independent positive association with IGI (standardized ß=0.242, P<0.001). Additionally, both HbA1c and GA were independently correlated with HOMA-IR and HOMA-ß. CONCLUSIONS: 1,5-AG is not only correlated with basal insulin sensitivity and secretion, but also closely associated with early-phase insulin secretion in Chinese patients with newly diagnosed type 2 diabetes mellitus.