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Visfatin is identified a pro-inflammatory cytokine and its serum level is increased in various cancers. This study aimed to evaluate the prognostic value of preoperative serum visfatin level in breast cancers. Preoperative serum visfatin levels of 248 patients with breast cancer and serum visfatin levels of 100 healthy individuals and 100 benign women controls were determined using enzyme-linked immunosorbent assay. Unfavorable outcome was defined as first local recurrence, distant metastasis, second primary cancer of another organ, or death from any cause. Disease-free survival was defined as the time between surgery and the date of unfavorable outcome whichever appeared first. Overall survival was defined from surgery to death for any cause. The association of serum visfatin level with outcomes including mortality, unfavorable outcome, disease-free survival and overall survival was investigated by univariate and multivariate analyses. Preoperative serum visfatin level was substantially higher in patients than in healthy subjects and benign controls respectively. Elevated preoperative serum level of visfatin was identified an independent predictor of mortality, unfavorable outcome, disease-free survival and overall survival. Receiver operating characteristic curve analysis showed that serum level visfatin had high predictive value for mortality and unfavorable outcome. Thus, our results suggest that high preoperative serum visfatin level is associated with poor patient outcomes as well as may play a role as prognostic biomarker in breast cancer survival.

To observe the therapeutic effect of oblique needling in combination with Tuina at the sacroiliac joint for patients experiencing sacroiliac joint injury.One hundred and twenty patients with sacroiliac joint injury were randomized into routine Tuina group and oblique needling combined with Tuina (Acu+ Tuina) group (n = 60 in each group). For patients of the Tuina group, routine Tuina as rotating, pressing-rubbing, digital pressing, articular moving, etc. was manipulated at Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 31), Xialiao (BL 30), Huantiao (GB 30), Zhibian (BL 54), Weizhong (BL 40) and sacroiliac joint area. For patients of the Acu+Tuina group, the anatomical points between the bilateral iliac crests and the sacral joints were punctured obliquely with disposable acupuncture needles. The treatment was conducted for 30 min every time, once daily for 3 weeks except weekends. The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI, concerning intensity of pain, lifting, ability to care for oneself, ability to walk, ability to sit, sexual function, ability to stand, social life, sleep quality, and ability to travel) were employed to evaluate the patients' reactions and functional activity changes before and after the treatment.Following the treatment, of the two 60 patients in the Tuina and Acu + Tuina groups, 12 and 26 cases were cured, 20 and 20 experienced marked improvement, 16 and 11 were effective, 12 and 3 invalid, with the effective rates being 80% and 95%, respectively. The effective rate of the Acu+ Tuina group was significantly superior to that of the Tuina group (P0.05). The VAS scores and OD were considerably decreased in both groups after the treatment and were significantly lower in the Acu+Tuina group than in the Tuina group (P0.01).Oblique needling the anatomical points in the sacroiliac joint region combined with Tuina manipulation is evidently better than simple Tuina in reducing pain and in improving functional activity and life quality in sacroiliac joint injury patients.

Objective To compare the effectiveness of first trimester, second trimester, and integrated screening for Down's syndrome. Setting Two prenatal diagnosis centres in China. Methods A total of 11,966 pregnant women (≥18 years) were screened over 21 months. First trimester screening (11–13 weeks) comprised measurement of serum free beta-human chorionic gonadotrophin (β-hCG) and pregnancy-associated protein-A concentrations, and fetal nuchal translucency thickness. Second trimester screening (15–20 weeks) comprised measurement of β-hCG and alpha fetoprotein concentrations. Computer software was used to calculate the risk of carrying a Down's syndrome fetus. Results The overall incidence of Down's syndrome was 0.2% (23/11,966). When the false-positive rate was fixed at 5%, detection rates for first trimester, second trimester, and integrated screening were 73.9%, 69.6%, and 82.6%, respectively. When the false-positive rate was fixed at 3%, detection/sensitivity rates for first trimester, second trimester, and integrated screening were 65.2%, 56.5%, and 73.9%, respectively. Conclusions These findings suggest that integrated screening was the most effective means of screening for Down's syndrome in a Chinese population.

This paper presents OntoRT, an ontology model for Role-base Trust-management(RT) framework, which covers a large fragment of RT including RT0, RT1, RT2 and application domain specification documents (ADSDs). RT addresses distributed authorization problems in decentralized collaborative systems. OntoRT establishes a common vocabulary for RT roles and policies across domains. We describe OntoRT formally in Description Logic(DL) SHOIN(D) and DL-safe SWRL rules. Basing on our logical formalization it is feasible to authorize and analyze RT policies automatically via the state of arts DL reasoners. Finally, we show how OntoRT can be integrated with OWL-DL ontologies which are W3C standard for representing information on the Web. By referring to OWL-DL ontologies that provide rich domain knowledge, specification and management of RT policies are simplified.

Based on some results of the fuzzy network computation and competitive analysis, the Online Fuzzy Most Reliable Path Problem (OFRP), which is one of the most important problems in network optimization with uncertainty, has been originally proposed by our team. In this paper, the preliminaries about fuzzy and the most reliable path and competitive analysis are given first. Following that, the mathematical model of OFRP, in which two kinds of uncertainties, namely online and fuzzy, are combined to be considered at the same time, is established. Then some online fuzzy algorithms are developed to address the OFRP and the rigorous proofs of the competitive analysis are given in detail. Finally, some possible research directions of the OFRP are discussed and the conclusions are drawn.

CD44 is a multifunctional protein involved in cell adhesion and signaling. The role of CD44 in prostate cancer (PCa) development and progression is controversial with studies showing both tumor-promoting and tumor-inhibiting effects. Most of these studies have used bulk-cultured PCa cells or PCa tissues to carry out correlative or overexpression experiments. The key experiment using prospectively purified cells has not been carried out. Here we use FACS to obtain homogeneous CD44(+) and CD44(-) tumor cell populations from multiple PCa cell cultures as well as four xenograft tumors to compare their in vitro and in vivo tumor-associated properties. Our results reveal that the CD44(+) PCa cells are more proliferative, clonogenic, tumorigenic, and metastatic than the isogenic CD44(-) PCa cells. Subsequent molecular studies demonstrate that the CD44(+) PCa cells possess certain intrinsic properties of progenitor cells. First, BrdU pulse-chase experiments reveal that CD44(+) cells colocalize with a population of intermediate label-retaining cells. Second, CD44(+) PCa cells express higher mRNA levels of several 'stemness' genes including Oct-3/4, Bmi, beta-catenin, and SMO. Third, CD44(+) PCa cells can generate CD44(-) cells in vitro and in vivo. Fourth, CD44(+) PCa cells, which are AR(-), can differentiate into AR(+) tumor cells. Finally, a very small percentage of CD44(+) PCa cells appear to undergo asymmetric cell division in clonal analyses. Altogether, our results suggest that the CD44(+) PCa cell population is enriched in tumorigenic and metastatic progenitor cells.

To analyze the clinical effect of fetal chromosomal reciprocal translocation in order to optimize procedures for prenatal diagnosis and clinical counseling.Conventional G-banding karyotype analysis was performed on 7901 amniotic fluid samples. For fetuses found to have carried a reciprocal translocation, karyotypes of their parents were checked. Fetuses with de novo translocations also underwent microarray analysis to exclude small deletions, and were subjected to prenatal ultrasound monitoring till birth and one year follow-up. Those with de novo translocations were followed till 3 years old.A total of 24 fetal reciprocal translocations have been identified, which gave a detection rate of 0.30%. Analysis of parental karyotypes has found reciprocal translocations in 17 cases, including 9 maternal and 8 paternal cases. The remaining 4 were of de novo mutations, for which parental examination was refused in three cases. For fetuses with inherited translocations, prenatal ultrasound monitoring and follow-up results were all normal. For those with de novo translocations, although gene chip analysis has failed to detect copy number variations (CNVs), prenatal ultrasound and follow-up results had found three with abnormal outcome. These included 1 case with reciprocal translocation involving the X chromosome and an autosome.For prenatally detected reciprocal chromosome translocations, parental origin should be traced. Gene chip analysis can help to exclude small deletions and duplications. However, ultrasound monitoring and follow-up after birth are equally important. Based on comprehensive analysis of the results of combined testing, accurate counseling can be provided.

Carbachol-stimulated insulin release in the RINm5F cell is associated with elevation of the cytosolic Ca2+ concentration ([Ca2+]i) through mobilization of Ca2+ from thapsigargin-sensitive intracellular stores and with the generation of diacylglycerol (DAG). Thus carbachol activates phospholipase C, and this was thought to be the means by which it stimulates insulin secretion. However, when the elevation of [Ca2+]i was blocked by thapsigargin, the effect of carbachol to stimulate insulin release was unchanged. Thus the effect of carbachol to increase [Ca2+]i was dissociated from the stimulation of release. When the role of protein kinase C (PKC) was examined, carbachol-stimulated insulin release was found to be unaffected by phorbol ester-induced downregulation of PKC, using 12-O-tetradecanoylphorbol-13-acetate (TPA), and by the PKC inhibitors staurosporine, bisindolylmaleimide, and 1-O-hexadecyl-2-O-methylglycerol (AMG-C16). These treatments abolished the stimulation of release by TPA. Thus the carbachol activation of PKC appeared also to be dissociated from the stimulation of insulin release. However, when the activation of several different PKC isozymes was studied, an atypical PKC isozyme, zeta, was found to be translocated by carbachol. By Western blotting analysis, carbachol selectively translocated the conventional PKC isozymes alpha and beta (the activation of which is dependent on Ca2+ and DAG) from the cytosol to the membrane. Carbachol also translocated the atypical PKC isozyme zeta, which is insensitive to Ca2+, DAG, and phorbol esters. The PKC inhibitors staurosporine, bisindolylmaleimide, and AMG-C16 blocked the stimulated translocation of PKC-alpha and -beta, but not that of PKC-zeta. Prolonged treatment of the cells with TPA downregulated PKC-alpha and -beta, but not PKC-zeta. Under all these conditions, carbachol-stimulated insulin release was unaffected. However, a pseudosubstrate peptide inhibitor specific for PKC-zeta inhibited the translocation of PKC-zeta and 70% of the carbachol-stimulated insulin secretion. The data indicate that carbachol-stimulated insulin release in RINm5F cells is mediated to a large degree by the activation of the atypical PKC isozyme zeta.

To determine the origin of 1 prenatally detected small supernumerary marker chromosome (sSMC) using SNP-chip technology, and to deduce the underlying mechanism.The fetal sample was subjected to karyotype analysis. The identified sSMC was subjected to genom wide scan using a SNP microarray chip. The results were validated with fluorescence in situ hybridization (FISH).The karyotype of the fetus was determined as 46, X, +mar, which was verified by SNP microarray chip analysis as Yp11.2-11.3 duplication, along with loss of Yq11.2 region, FISH analysis has confirmed that the sSMC has derived from the Y chromosome.The karyotype of the fetus was determined as 46, X, idic(Y) (pter→ p11.2::11.2→ pter). Regional deletion of Yq11.2 has been associated with male azoospermia. SNP chip analysis can exclude minor deletions and duplications with a size of more than 1 Mb, which may be applied for verifying difficult cases as well as microdeletion and duplication syndromes upon prenatal diagnosis.

Galanin decreased short circuit current (Isc) and increased active Na+ and Cl- absorption in rabbit ileum. In the absence of calcium, the galanin-induced decrease in Isc was inhibited by approximately 60%. Tetrodotoxin significantly reduced the effect of galanin on Isc, and tetrodotoxin and EGTA totally blocked the effect, indicating that the nonneuronal mediator of the effect is Ca2+ dependent. Galanin binding to basolateral membranes prepared from ileal epithelial cells was specific and of high affinity. These results suggest the involvement of this peptide in the regulation of intestinal epithelial cell function.

To assess the diagnostic value of multiplex ligation-dependent probe amplification (MLPA) for detection of common chromosome aneuploidy in amniotic fluid (AF) cells in order to obtain an accurate, rapid, cost-effective and high-throughput method in routine prenatal clinical practice.The MLPA test was performed on 500 AF samples by using kit P095 and the results were obtained by using analysis software RH-MLPA-v511. The results were compared with that from fluorescence in situ hybridization (FISH) and traditional karyotyping (TK). The technical critical issues were analyzed in routine diagnostic application.The absolute specificity and sensitivity of the MLPA test to detect the aneuploidy were 100%. For the 500 AF samples, the success rate of the MLPA tests was 97%. Among them 92% were finished within three working days and 5% required more days for repeating. The test failure rate was 3%. The results confirmed that for the 38 detectable aneuploid samples, the probe reliability weighted mean ratio values were more than 4SD compared to normal diploids and the 2 suspected trisomy samples were more than 2SD. In this study, authors analyzed hybridization efficiencies of 8 probes for chromosome 21, and the presence of a trisomy was considered if at least 4 of the 8 probes gave probe ratio of1.3.Thedata suggested that MLPA is a rapid, simple and reliable method for large scale testing for aneuploidy of chromosomes 13, 18, 21, X, or Y in AF. The MLPA technology is complementary to AF culture and valuable for prenatal diagnosis.

A user authentication scheme based upon the properties of Euclidean geometry properties is proposed. The center authority (CA) constructs the shared information by using both its secret and the userpsilas password in the user registration phase. Then the request message is computed by using both the userpsilas password and the registered information based on properties of Euclidean geometry and one-way hash functions. In the system verification phase, the CA verifies the validity of a user based on its request message and the CApsilas secrets. Only the CA can do the verification because only it knows its secret. The verification is fast because it does not need to access the database and its computation is simple. The timestamp allows the proposed scheme to withstand replay attacks. The security analysis shows that our scheme is also secure against eavesdropping attacks, and dictionary attacks. A formal approach is adopted to prove the proposed scheme is secure. The experimental results show that our scheme is more applicable for large-scale network environments than a password-based system or a PKI certificate-based system.

To investigate the effect of trabeculectomy combined with amniotic membrane and extracellular matrix (ECM) of conjunctiva on filtering bleb in rabbits.Glaucoma was induced by injecting alpha-chymotrypsin into the posterior chamber of rabbit eyes. 27 rabbits were randomly divided into the following three groups: group (1) trabeculectomy alone as control; group (2) trabeculectomy combined with amniotic membrane transplantation; group (3) trabeculectomy combined with extracellular matrix (ECM) transplantation. IOPs were measured by a Schiötz tonometer and filtering bleb observed under a microscopy and electric microscopy at day 1, 7, 14, 21, 28, 35, 42, 56 after surgery.Compared with pre-operation, the IOP in the control group (group 1) was reduced from (34.59 +/- 4.44) mm Hg (1 mm Hg = 0.133 kPa) to (11.31 +/- 2.76) mm Hg, (19.20 +/- 5.27) mm Hg, (21.17 +/- 4.36) mm Hg, (22.22 +/- 1.39) mm Hg, (23.90 +/- 1.97) mm Hg, (23.67 +/- 1.73) mm Hg, respectively, after surgery. In the group 2, the IOP was decreased from (34.38 +/- 4.21) mm Hg to (10.48 +/- 2.45) mm Hg, (12.80 +/- 3.41) mm Hg, (13.50 +/- 2.25) mm Hg, (16.17 +/- 1.73) mm Hg, (17.22 +/- 1.32) mm Hg, (16.71 +/- 1.52) mm Hg, respectively. In the group 3, the IOP was decreased from (34.66 +/- 4.49) mm Hg to (10.94 +/- 2.75) mm Hg, (11.29 +/- 2.40) mm Hg, (13.93 +/- 3.55) mm Hg, (15.63 +/- 3.54) mm Hg, (15.70 +/- 2.44) mm Hg, (15.12 +/- 3.65) mm Hg, respectively, at day 1, 7, 14, 28, 42, 56, post-operatively. IOPs in the group 2 and 3 were significantly (P0.01) lower than that in the control group (group 1) at post-operative day 7, 14, 28, 42, 56. However, there was no IOP difference between the group 2 and 3 post-operatively at any time. Morphologically, the filtering blebs were flatded at day 28 in the group 1, while were normal in the group 2 and 3 at day 56. Less scar formation of filtering blebs was observed in group 2 and 3 compared with group 1.Trabeculectomy combined with the application of amniotic membrane or conjunctiva ECM can improve filtering bleb function and reduce scar formation that lead to a better IOP control after surgery.

Based on some results of the fuzzy network computation and competitive analysis, the On-line Fuzzy Most Reliable Path Problem (OFRP) is originally proposed by our team. In this paper, the preliminaries about the fuzzy most reliable path and competitive analysis are given first. Following that, the mathematical model of OFRP is established. In this realistic model, two kinds of uncertainties, namely on-line and fuzzy, are combined to be considered at the same time. Then some on-line fuzzy algorithms are developed to address the OFRP and the rigorous proofs of the competitive analysis are given in detail. Finally, some possible research directions about the OFRP are discussed and the conclusions are made.

BH3 (Bcl-2 homology 3)-only proteins of the Bcl-2 family play an essential role in apoptosis. In this study, a novel human BH3-only protein, Bcl-2-interacting mediator (Bim)gamma, was identified during our study of regulation of prostate cancer cell death by Bcl-2 family proteins. Bimgamma shares the highest amino acid sequence homology to BimEL and BimL, two proapoptotic BH3-only Bcl-2 proteins derived from alternative mRNA splicing. Genomic studies indicate that Bimgamma is a novel splice variant of Bim and is generated as a result of the retention of a 126-bp intron of the bim gene. Bimgamma mRNA displays a tissue-specific expression pattern distinct from those of the other Bim isoforms. Subcellular fractionation studies indicate that Bimgamma is localized both in intracellular membranes and cytosol. Interestingly, Bimgamma mRNA, similar to the BimEL protein, is up-regulated in the majority of the prostate cancer cell lines studied, whereas several other proapoptotic Bcl-2 proteins, including Bax, Bak, and Bad, are down-regulated in prostate cancer cells. Functional studies indicate that Bimgamma inhibits clonal growth in prostate cancer cells and promotes apoptosis, which is inhibited by overexpressing Bcl-2. Because both Bimgamma and BimEL are proapoptotic BH3-only proteins and both are up-regulated in prostate cancer cells, they may play a unique role in prostate cancer development.

Carbachol can stimulate insulin release in RINm5F cells by a mechanism that does not involve the elevation of cytosolic free Ca2+ concentrations or the activation of conventional protein kinase Cs (Mol Pharmacol 47:863–870, 1995). Thus, a novel signal transduction pathway links the muscarinic activation of the cells to increased insulin secretion. The question arises as to whether the pathway results from a novel receptor, different from the five established muscarinic receptors, or whether a “normal” receptor in the RINm5F cell activates a novel pathway. To distinguish between these two possibilities, the muscarinic receptors in the RINm5F cell were identified. Using polymerase chain reaction, combined with subcloning and DNA sequencing techniques, the cDNAs that encode the established M3 and M4 receptors were identified. The cDNAs for the M1, M2, and M5 receptors were not found. Pharmacological studies showed a rank order of potency for muscarinic receptor subtype antagonists to inhibit carba-chol-induced insulin release (half-maximal inhibitory concentration [pIC50] values given in parentheses): atropine (nonselective, 9.0) > 4-diphenyl-acetoxy-iV-methyl piperidine methiodide (M3/M1, 8.6) > para-fluoro-hexahydrosiladiphenidol (M3, 8.1) > hexahydrosiladiphenidol (M3, 8.0) > tropicamide (M4, 6.4) > pirenzepine (M1, 6.1) > methoctramine (M2, 5.9). This antagonist profile suggests that it is the M3 receptor that mediates carbachol-induced insulin release. In this case, the novel signaling involved in the unusual carbachol response would not be due to a novel receptor but to the well-characterized M3 receptor. It appears, therefore, that the novel portion of the signaling pathway lies downstream of the M3 receptor and may consist of products of phosphatidylinositol hydrolysis, other than inositol triphosphate and diacylglycerol, resulting from the activation of phospholipase C. While a contributory role of the M4 receptor cannot be ruled out, there is no evidence in its favor other than its presence in the cell.

IntroductionMolecular testing for detection of epithelial and/or breast-specific mRNA has the potential to aid in the comprehensive examination of axillary lymph nodes (ALNs) in breast cancer. We evaluated the performance of a One-Step Nucleic Acid Amplification assay (OSNA; Sysmex), an automated assay for detection of cytokeratin 19 mRNA in chemotherapy(CT)-naive and -treated ALNs of breast cancer patients using conventional histopathologic examination (HE) as the gold standard.METHODSALNs obtained from complete axillary dissections were serially sectioned at 1-mm intervals using a proprietary lymph node cutter (Sysmex), and alternate slices were used for OSNA and HE, which included one hematoxylin and eosin stain and a pancytokeratin (CK) immunostain. Isolated tumor cells were classified as micrometastases (MiM) in CT-treated ALNs and as negative in CT-naive ALNs. The presence of tumor cells in either stained preparation was used for categorization of metastatic carcinoma. The agreement between OSNA and HE results for detection of metastatic carcinoma was estimated by using the kappa coefficient for CT-treated and -naive ALN groups separately.RESULTSWe studied 279 ALNs from 39 patients with breast cancer; these included 162 CT-treated and 117 CT-naive ALNs. In the CT-naive group, metastatic carcinoma was detected by HE in 15 of the 117 ALNs (12.8%), 7 classified as micrometastases and 8 as macrometastases. All but 3 of the 7 micrometastases were detected by OSNA. The kappa coefficient between HE and OSNA for this group was 0.87 (95% confidence interval [CI], 0.72–1.00) which implies near perfect agreement between the two methods. In the 162 CT-treated ALNs, metastatic carcinoma was detected in 44, 13 classified as micrometastases and 31 as macrometastases. The results for 17 ALNs in the CT-treated group were discordant between the two methods: 3 ALNs were considered positive by OSNA but negative by HE; 10 ALNs with a mean size of metastasis of 0.5 mm (MiM) and 4 with a mean size of metastasis of 2 mm (macrometastases) were considered positive by HE and negative by OSNA. The kappa coefficient between the two methods for this group was estimated to be 0.71 (95% CI, 0.58–0.84) which implies substantial agreement between the two methods for this group.CONCLUSIONS1. The detection of metastatic carcinoma was highly comparable between the OSNA assay and conventional HE in both CT-naive and -treated ALNs in breast cancer.2. The minimal discordance between HE and OSNA in the results for detection of very small metastases in ALNs in both CT-naïve and –treated groups was most likely the result of tissue-allocation bias.3. The OSNA assay has the potential to be used as either a stand-alone test or integrated with conventional HE for the comprehensive examination of ALNs in breast cancer, thus likely improving current methods of evaluation of ALNs for more accurate axillary staging. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1012.