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We explored the redox status of beta 2 glycoprotein I (β2GPI) in different stages of diabetic angiopathy. Type 2 diabetes mellitus (T2DM) had a significantly lower proportion of reduced β2GPI as compared to healthy controls (p<0.05). There was a trend that the mild coronal atherosclerosis heart disease (CAD) had higher proportion of reduced β2GPI than non-CAD and severe-CAD groups, however without significances (p>0.05). The mild-A-stenosis group and mild-diabetic retinopathy (DR) groups had higher proportion of reduced β2GPI than their severely affected counterparts. The mild-slow nerve conduction velocity (NCVS) group had higher proportion of reduced β2GPI than normal nerve conduction velocity (NCVN group) and severe-NCVS groups. The proportion of reduced β2GPI was in positive correlation with 24 h urine microalbumin and total urine protein, and the proportion of reduced β2GPI was in negative correlation with serum and skin advanced glycation end products (AGEs). Taken together, our data implicate that the proportion of reduced β2GPI increased in the early stage of angiopathy and decreased with the aggravation of angiopathy. [ABSTRACT FROM AUTHOR]

Objective Beta-2-glycoprotein I (β2GPI) constitutes the major autoantigen in the antiphospholipid syndrome (APS), a common acquired cause of arterial and venous thrombosis. We recently described the novel observation that β2GPI may exist in healthy individuals in a free thiol (biochemically reduced) form. The present study was undertaken to quantify the levels of total, reduced, and posttranslationally modified oxidized β2GPI in APS patients compared to various control groups. Methods In a retrospective multicenter analysis, the proportion of β2GPI with free thiols in serum from healthy volunteers was quantified. Assays for measurement of reduced as well as total circulating β2GPI were developed and tested in the following groups: APS (with thrombosis) (n = 139), autoimmune disease with or without persistent antiphospholipid antibodies (aPL) but without APS (n = 188), vascular thrombosis without APS or aPL (n = 38), and healthy volunteers (n = 91). Results Total β2GPI was significantly elevated in patients with APS (median 216.2 μg/ml [interquartile range 173.3-263.8]) as compared to healthy subjects (median 178.4 μg/ml [interquartile range 149.4-227.5] [ P < 0.0002]) or control patients with autoimmune disease or vascular thrombosis (both P < 0.0001). The proportion of total β2GPI in an oxidized form (i.e., lacking free thiols) was significantly greater in the APS group than in each of the 3 control groups (all P < 0.0001). Conclusion This large retrospective multicenter study shows that posttranslational modification of β2GPI via thiol-exchange reactions is a highly specific phenomenon in the setting of APS thrombosis. Quantification of posttranslational modifications of β2GPI in conjunction with standard laboratory tests for APS may offer the potential to more accurately predict the risk of occurrence of a thrombotic event in the setting of APS. [ABSTRACT FROM AUTHOR]

High serum beta 2 glycoprotein I (β2GPI) is associated with complications of type 2 diabetes mellitus (DM), and especially microvascular disorders. In contrast, reduced β2GPI (Rβ2GPI) can prevent diabetic vascular injury. This study aimed to investigate the protective function of Rβ2GPI in DM vascular disorders, and to assess the under lying mechanisms. High glucose-induced injury in human umbilical vein endothelial cells (HUVECs) was used to model hyperglycemia. Alow concentration of Rβ2GPI (0.5 μM), but not β2GPI, mitigated high glucose-induced cell injury. High glucose decreased miR-21 expression and Akt phosphorylation at 6 h, but facilitated their expression at 48 h. Moreover, high glucose decreased phosphatase and tensin homolog deleted on chromosome ten(PTEN) expression at 6 h, but facilitatedits expression at 48 h. Importantly, by promoting miR-21 expression, Rβ2GPI mitigated high glucose-induced PTEN expression, reduced Akt phosphorylation and nitric oxide synthase activity, and increased cyclooxygenase-2 activity and cell loss. Similar to Rβ2GPI, an miR-21 mimic (1 pM) and PTEN inhibition (1 μM bpV, or PTEN silencing) exerted protective action, while an Akt signaling pathway inhibitor (LY294002, 1 μM) aborted the effect of Rβ2GPI on high glucose-induced cell injury. Finally, Rβ2GPI inhibited high glucose-induced apoptosis via a mitochondria-dependent pathway. These data reveal that Rβ2GPI exerts protective action in high glucose-induced HUVEC injury. The mechanism is related to the miR-21-PTEN-Akt pathway and mitochondria-dependent apoptosis. This study provides in vitro data supporting the therapeutic effect of Rβ2GPI in diabetic vascular injury., Competing Interests: None.

Type 2 diabetes mellitus induced atherosclerosis (DA) is regarded as a major cause of disability and death in diabetic patients. The early prediction of atherosclerosis in patients DM is necessary. Therefore, we aimed to identify special plasma microRNAs that can serve as a novel non-invasive screening signature of DA patients with atherosclerosis and test its specificity and sensitivity in the early diagnosis of DA. In total, we obtained plasma samples from 285 diabetic atherosclerosis patients and matched diabetic retinopathy (DR) patients, diabetic nephropathy (DN) patients, diabetes mellitus without complication (DM) and healthy controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA). Three miRNAs were significantly increased in patients with DA compared with other groups after the multiple stages. The areas under the receiver operating characteristic (AUC) curves of the validated three-plasma miRNAs signature in DA comparing with NC were 0.881, 0.709 and 0.842 while the merged was 0.940 while DA comparing with DM was 0.879, 0.663, 0.731 and the merged was 0.928. The three miRNA could also distinguish DA from DN with an AUC of 0.894, 0.782, 0.910 and 0.963 (merged) as well as from DR with an AUC of 0.876, 0.815, 0.850 and 0.925 (merged). In conclusion, these data provide evidence that plasma miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of DA. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of DA from DR, DN, DM patients.

We explored the redox status of beta 2 glycoprotein I ( β 2 GPI) in different stages of diabetic angiopathy. Type 2 diabetes mellitus (T2DM) had a significantly lower proportion of reduced β 2 GPI as compared to healthy controls ( p < 0.05). There was a trend that the mild coronal atherosclerosis heart disease (CAD) had higher proportion of reduced β 2 GPI than non-CAD and severe-CAD groups, however without significances ( p > 0.05). The mild-A-stenosis group and mild-diabetic retinopathy (DR) groups had higher proportion of reduced β 2 GPI than their severely affected counterparts. The mild-slow nerve conduction velocity (NCVS) group had higher proportion of reduced β 2 GPI than normal nerve conduction velocity (NCVN group) and severe-NCVS groups. The proportion of reduced β 2 GPI was in positive correlation with 24 h urine microalbumin and total urine protein, and the proportion of reduced β 2 GPI was in negative correlation with serum and skin advanced glycation end products (AGEs). Taken together, our data implicate that the proportion of reduced β 2 GPI increased in the early stage of angiopathy and decreased with the aggravation of angiopathy.

Aim: To investigate the relationship between serum vitamin D3 levels and liver fibrosis or inflammation in treatment-naive Chinese patients with chronic hepatitis C (CHC)., Methods: From July 2010 to June 2011, we enrolled 122 CHC patients and 11 healthy controls from Dingxi city, Gansu Province, China. The patients were infected with Hepatitis C virus (HCV) during blood cell re-transfusion following plasma donation in 1992-1995, and had never received antiviral treatment. At present, all the patients except two underwent liver biopsy with ultrasound guidance. The Scheuer Scoring System was used to evaluate hepatic inflammation and the Metavir Scoring System was used to evaluate hepatic fibrosis. Twelve-hour overnight fasting blood samples were collected in the morning of the day of biopsy. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, cholinesterase, prothrombin activity, albumin, γ-glutamyl transpeptidase, hemoglobin, calcium and phosphorus were determined. Serum HCV RNA levels were measured by real-time PCR. Serum levels of 25-hydroxyvitamin D3 [25(OH)D3] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were measured by high-performance liquid chromatography tandem mass spectrometry., Results: Serum levels of 25(OH)D3 but not 24,25(OH)2D3 were significantly lower in CHC patients than in control subjects. Serum 25(OH)D3 levels did not correlate with liver fibrosis, inflammation, patient age, or levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, prothrombin activity, cholinesterase or HCV RNA. However, serum 25(OH)D3 levels did correlate with serum 24,25(OH)2D3 levels. Serum 25(OH)D3 and 24,25(OH)2D3 levels, and the 25(OH)D3/24,25(OH)2D3 ratio, have no difference among the fibrosis stages or inflammation grades., Conclusion: We found that serum levels of 25(OH)D3 and its degradation metabolite 24,25(OH)2D3 did not correlate with liver fibrosis in treatment-naive Chinese patient with CHC.

Objective: To explore the recent clinical safety and efficacy of photoselective vaporization of prostate (120 W) for the treatment of large gland benign prostatic hyperplasia., Methods: The clinical data of 112 cases who accepted photoselective vaporization of prostate (120 W) for the treatment of severe benign prostatic hyperplasia (the weight of prostate > 75 g) from July 2010 to January 2012 was statistical analyzed. Relief symptoms and complications were observed around surgery, and the recent clinical efficacy was analyzed., Results: All the operations were smooth. There were not transurethral resection syndrome. No cases need transfusion intraoperative and postoperative. The operation average time was (52.6 ± 12.1) minutes, and the average amount of bleeding was (27.4 ± 18.5) ml. The postoperative bladder irrigating time was (19.4 ± 7.3) hours, the mean postoperative indwelling catheter time was (3.2 ± 0.6) days, and the mean postoperative hospital stay was (4.8 ± 1.3) days. Postoperative international prostate symptom score (t = 52.24 - 59.10), quality of life (t = 48.42 - 53.63), maximum flow rate (t = -31.01 - -24.23) and residual urine volume (t = 9.85 - 12.53) compared with preoperative are significantly improved (P < 0.01)., Conclusions: With the safe operation of photoselective vaporization of prostate (120 W) for the treatment of large gland benign prostatic hyperplasia, it is less bleeding, recent efficacy is significant, and it is especially appropriate to elderly patients at high risk of large gland.

The biodegradation of nonylphenol polyethoxylates (NPEOs) was studied under three different reductive conditions (methanogenesis, denitrification, and desulfuration conditions). Effects of organic matter and temperature on the biodegradation of NPEOs were also studied. The results showed that NP9EO could be rapidly biodegraded under three different reductive conditions. Gulcose and sodium acetate could inhibit NP9EO biodegradation while yeast extract could enhance the biodegradation. Temperature coefficients (u), which was relative with rate coefficient (k), under methanogenesis, denitrification, and desulfuration conditions were 19.93 kJ/mol, 23.13 kJ/mol, 27.00 kJ/mol respectively, when temperature ranged from 15 degrees C to 35 degrees C. The result suggested that the biodegradation rate constant of NP9EO under desulfuration condition was more sensitive to temperature than those of denitrification and methanogenesis treatments. These results could provide useful information on bioremendation of NPEOs contaminants.

Objective: To investigate the effects of high D-glucose on migration, proliferation, and angiogenesis of endothelial cells and to make sure whether PI3K and Akt signaling pathway plays an important role in the pathogenesis of diabetic vascular complications., Methods: Human umbilical vein endothelial cells (HUVECs) were cultured. D-glucose of the concentrations of 5 mmol/L, 15 mmol/L, and 30 mmol/L and mannitol of the concentrations of 5 mmol/L, 15 mmol/L, and 30 mmol/L were added in to the medium, the migration rate of the cells was measured by wound healing test and the cell proliferation was examined with CellTiter 96 AQ(ueous) One Solution cell proliferation assay. Matrigel was spread on 96-well plate, and culture of HUVECs with D-glucose and mannitol of different concentrations were added. Microscopic photography was used to calculate the total area of vascular bed, average vessel length, vessel number, branch points, so as to observe the angiogenesis. Immuno-precipitation was used to detect the expression of p85/PI3K. Western blotting was used to detect the protein expression of p85/PI3K, p-PI3K, GSK3beta (downstream kinase of Akt), p-Akt (Threonine308) and p-GSK3beta. LY294002, a PI3K inhibitor, of the concentrations of 0.1 micromol/L, 1 micromol/L, and 10 micromol/L was added into the culture fluid with 5 mmol/L D-glucose, then the endothelial cell migration, proliferation number, total area of blood bed, etc were observed., Results: The migration rate of the 5 mmol/L D-glucose group was 100 +/- 23/microm2, and D-glucose dose-dependently decreased the migration rate, e.g. the migration rates of the 15 mmol/L and 30 mmol/L D-glucose groups were 77 +/- 18/microm2 and 46 +/- 18/microm2 respectively, both significantly lower than that of the 5 mmol/L D-glucose group (both P < 0.01). LY294002 of the concentrations of 0.1 micromol/L, 1 micromol/L, and 10 micromol/L dose-dependently decrease the endothelial cells migration rates to 68 +/- 16/microm2, 36 +/- 12/microm2, and 13 +/- 3/microm2 respectively (all P < 0.01) The cell proliferation rate of the 5 mmol/L, 15 mmol/L) and 30 mmol/L D-glucose groups were 59,128 +/- 7415/well, 33,144 +/- 9082/well, and 11,625 +/- 4196/well respectively, showing that D-glucose dose-dependently decreased the cell proliferation (all P < 0.01). LY294002 of the concentrations of 0.1 micromol/L, 1 micromol/L, and 10 micromol/L dose-dependently decrease the endothelial cell proliferation to 42,560 +/- 4213/well, 17,688 +/- 7198/well, and 5704 +/- 558/well respectively (all P < 0.01). 15 mmol/L and 30 mmol/L D-glucose decreased the numbers of total area of vascular bed, average tubule length, number of capillaries, and number of vessel branch pint formed on the Matrigel. LY294002 dose-dependently inhibited the angiogenesis (P < 0.05 or P < 0.01) 15 mmol/L and 30 mmol/L D-glucose dose-dependently inhibited the phosphorylation of p85/P13K and Akt (P < 0.05 and P < 0.01). However, D-glucose did not influence the protein expression of p85/PI3K and Akt. Mannitol did not influence the cell proliferation, angiogenesis, and the expression of p85/PI3K, phosphorylated p85/PI3K, Akt, phosphorylated Akt (Thr308), and phosphorylated GSK3beta., Conclusion: Hyperglycemia-impaired PI3K-Akt signaling may lead to migration, proliferation and angiogenesis dysfunction of endothelial cells in diabetes patients, which is likely to contribute to the pathogenesis of diabetic vascular complications.

Objective: To study the characteristics of molecular typing and phylogenic relationship among the Vibrio cholerae serogroup O139 strains isolated from environment and sea food samples during cholera outbreaks, in Sichuan province in 2004 and to trace the source of infections so as to support the ascertainment of epidemic control strategy., Methods: Cholera toxin gene was detected by polymerase chain reaction amplification. Pulsed-field gel electrophoresis (PFGE) was used for subtyping of isolates and clustering of patterns was analysed with the software BioNumerics., Results: In all the 72 strains under analysis, 68 appeared to be toxigenic while 4 from river water derived isolates were toxin gene negative. Sixty-seven strains were clustered into 16 PFGE patterns when digested with Not I. The patterns of toxigeinc O139 strains isolated from turtles in the markets were identical with the patterns of strains appeared in the outbreaks respectively. The PFGE patterns of isolates from different outbreaks were inconsistent., Conclusion: The sources of infection causing these outbreaks were complicated. Contaminated turtles might also be one of the major sources of outbreaks when being served at the dinner parties in Sichuan in 2004.