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Objective: To investigate the influence of divalent cation chelator EDTA and heparin sodium on the detection of ITP platelet-specific autoantibodies by the modified monoclonal antibody immobilization of platelet antigen assay (MAIPA) and to explore the relationship between types of platelet specific autoantibodies and glucocorticoid efficacy., Methods: The samples were obtained from EDTA- and heparin- anticoagulant ITP patients, respectively, so as to detect the platelet-specific autoantibodies (GPIIb/IIIa and GPIbα) in 140 ITP samples by modified MAIPA, then the differences between these two methods were compared., Results: Out of 140 cases in EDTA group, 55 cases were positive for GPIIb/IIIa, while 76 cases in heparin group were positive for GPIIb/IIIa, 42 cases in both group were repeatable; among them 13 cases were positive in EDTA group and negative in heparin group, while 34 cases were positive in heparin group and negative in EDTA group, there was significant difference between them (x (2) = 9.38, P < 0.05), 62 cases in 140 cases of EDTA group were positive for GPIba, while 51 cases in heparin group were positive for GPIba, 42 cases in both group were repeatabe; among them 20 cases were positive in EDTA group and negative in heparin group, while 9 cases were positive in heparin group and negative in EDTA group, there was no significant difference between them (x (2) = 3.44, P > 0.05). A total of 320 cases received a standard glucocorticoid treatment, out of them 143 cases were positive for GPIbα with effective rate 39.9%, 177 cases were negative for GPIbα with effective rate 79.7%, there was statisticalty significant difference between them (x (2) = 53.115, P < 0.05)., Conclusion: EDTA anticoagulant (a divalent cation chelator) has a significant influence on detection of ITP platelet-specific autoantibodies (GPIIb/IIIa) by a modified MAIPA method and the GPIbα antibody positive may be one of the important factors that results in un-sensitivity of ITP patients to glucocorticoid treatment.

The similar L-arginine molecule aggregation has been found in L-arginine (LA) and L-arginine phosphate monohydrate (LAP) aqueous solutions. The special fluorescence emission at 380 nm of LA aggregates in LAP solution has been found, compared with the emission of LA solution at 415 nm, which has an obvious blue shift. By comparing the fluorescence spectra of several solutions for L-arginine and L-lysine salts, the interaction between phosphate and guanidine in LAP solution was considered to be the cause of its special fluorescence emission. Meanwhile, when LAP molecule formed in solution, the fluorescence emission wavelength and the UV absorption intensity at 296 nm of L-arginine solutions have mutated. Therefore, the group interaction involved by guanidine has changed the fluorescence properties of L-arginine aggregates in LAP solution, indicating that the specific interaction between phosphate and guanidine exists in LAP molecule., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: Advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic vascular complications. Recently, growing evidence has shown that AGEs could be involved in the pathogenesis of insulin resistance. It has also been suggested that circulating AGE are associated with insulin resistance in nondiabetic patients. This study investigated whether serum AGEs levels are associated with insulin resistance in nondiabetic patients with obstructive sleep apnea (OSA)., Methods: A total of 139 male nondiabetic patients with OSA were recruited for participation in the study. Serum AGE levels were examined using an enzyme-linked immunosorbent assay. Insulin resistance was determined using the homeostasis model assessment index (HOMA-IR)., Results: There was a significant correlation between serum AGEs and the apnea-hypopnea index (AHI) (r = 0.281, p = 0.014), duration of SaO₂ < 90% (r = 0.267, p = 0.018), minimum SaO₂ (r = -0.188, p = 0.046), high-sensitivity C-reactive protein (hsCRP) (r = 0.274, p = 0.012), and HOMA-IR (r = 0.303, p < 0.001). Multiple regression analysis showed that serum AGEs (p = 0.011), AHI (p = 0.024), waist circumference (p = 0.040), and hsCRP (p = 0.046) were independently associated with HOMA-IR (R(2) = 0.392). In addition, the strength of the correlation between serum AGEs and HOMA-IR was related to the severity of OSA., Conclusions: The present study indicated that serum AGE levels were associated with insulin resistance in male nondiabetic patients with OSA. These findings suggest that AGEs may play a role in insulin resistance in OSA and may also be a biomarker for patients with OSA with high risk of developing type 2 diabetes.

Background: Osteosarcoma is the most common of all the bone malignancies and accounts for 30-80% of the primary skeletal sarcomas. The overall survival rate of patients with osteosarcoma is < 20% suggesting poor prognosis., Methods: The present study demonstrates the effect of retinoic acid chlorochalcone (RACC) incorporated glycol chitosan (GC) nanoparticle transfection in osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were transfected with various concentrations of RACC-incorporated GC nanoparticle for 24 h. The effect on cell proliferation, Ezh2 expression, apoptosis, cell cycle arrest, cell migration and invasiveness, Akt phosphorylation and local tumour growth and metastases were studied., Results: MG-63 and Saos-2 osteosarcoma cells on RACC-incorporated GC nanoparticle transfection for 24 h showed a concentration-dependent inhibition of cell proliferation. Of the various concentrations of RACC tested, the effective concentration started from 5 μM with an IC50 of 20 μM. Wound healing assay also showed that RACC-incorporated GC nanoparticles inhibited migration of tumor cells more effectively compared to the parent RA. RACC transfection resulted in inhibition of cell proliferation, Ezh2 expression inhibition, apoptosis through mitochondrial pathway by decrease in membrane potential and release of cytochrome c and cell cycle arrest in the G0/G1 phase. The invasiveness of cells treated with 5 and 20 μM RACC was decreased by 49 and 76% respectively, compared to the control. RACC-treated mice showed significantly lower number of metastases compared to that in the control mice., Conclusions: Thus, RACC-incorporated glycol chitosan nanoparticle strategy can be promising for the treatment of osteosarcoma.

Ovarian cancer remains the disease with the highest associated mortality rate of gynecologic malignancy due to cancer metastasis. Rearrangement of actin cytoskeleton by cytoskeleton protein plays a critical role in tumor cell metastasis. MICAL-L2, a member of MICAL family, can interact with actin-binding proteins, regulate actin cross-linking and coordinate the assembly of adherens junctions and tight junctions. However, the roles of MICAL-L2 in tumors and diseases have not been explored. In this study, we found that MICAL-L2 protein is significantly up-regulated in ovarian cancer tissues along with FIGO stage and associated with histologic subgroups of ovarian cancer. Silencing of MICAL-L2 suppressed ovarian cancer cell proliferation, migration and invasion ability. Moreover, silencing of MICAL-L2 prevented nuclear translocation of β-catenin, inhibited canonical wnt/β-catenin signaling and induced the mesenchymal-epithelial transition (MET). Taken together, our data indicated that MICAL-L2 may be an important regulator of epithelial-mesenchymal transition (EMT) in ovarian cancer cells and a new therapeutic target for interventions against ovarian cancer invasion and metastasis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aim: To discover antagonists of the orphan G-protein coupled receptor GPR139 through high-throughput screening of a collection of diverse small molecules., Methods: Calcium mobilization assays were used to identify initial hits and for subsequent confirmation studies., Results: Five small molecule antagonists, representing 4 different scaffolds, were identified following high-throughput screening of 16 000 synthetic compounds., Conclusion: The findings provide important tools for further study of this orphan G-protein coupled receptor.

We aimed to investigate the characteristics of bacterial profiles and antibiotic sensitivity in diabetic foot ulcers before and after wound bed preparation. This study involved 423 diabetic patients with Wagner grades 1 to 4 foot ulcers. Secretion culture was performed before wound bed preparation. The observation endpoint was when the wound showed a tendency toward healing and a specialist determined that stopping antibiotic treatment would not affect wound healing. A second secretion culture was performed after the observation endpoint. We obtained results from both secretion cultures from 411 patients. The proportion of multi-drug-resistant (MDR) gram-positive bacteria was 22.0% and 47.8% before and after treatment, respectively; that for gram-negative bacteria was 3.5% and 19.2%, respectively (P < .05). Pretreatment antibiotic sensitivity of staphylococci and other gram-positive bacteria was 48.7% and 44.8%, respectively; the rates decreased significantly after treatment to 36.8% (P = .031) and 34.8% (P = .027), respectively. Pretreatment antibiotic sensitivity of common and nonfermenting rare gram-negative bacteria was 55.4% and 54.6%, respectively, which decreased substantially after treatment to 33.2% (P = .002) and 32.9% (P = .003), respectively. Wound healing was achieved in 92.7% of patients. Pretreatment and posttreatment C-reactive protein levels were 124.759 ± 71.58 mg/dL and 82.8 ± 53.61 mg/dL, respectively (P < .05). In conclusion, following wound bed preparation for diabetic foot ulcers, MDR bacteria numbers were increased and antibiotic sensitivity was decreased; inflammation was decreased. These findings warrant future studies for confirmation., (© The Author(s) 2015.)

Background: The aim of this meta-analysis was to investigate possible relationships between bariatric surgery and incidence of obesity-related cancers. Obesity is an established risk factor for obesity-related cancers but the effects of bariatric surgery on incidence of obesity-related cancers are uncertain., Material/methods: We searched 4 electronic databases to identify eligible studies: PubMed, Embase, Web of Science, and Google Scholar. Five observational studies were eligible and included in this meta-analysis. Random-effects or fixed-effects odds ratio (OR) and its corresponding 95% confidence interval (CI) were pooled., Results: Meta-analysis of these 5 observational studies revealed that bariatric surgery was associated with a significantly (p=0.0004) reduced incidence of obesity-related cancers (OR=0.43, 95%CI, 0.27-0.69) when compared with control individuals. Pooled estimated data showed that bariatric surgery is associated with a 24% lower colorectal cancer (CRC) risk. No publication bias was detected by Egger's or Begg's tests., Conclusions: Although bariatric surgery may significantly reduce incidence of obesity-related cancers, considering the limitations of these included studies, these findings should be confirmed by further well-designed studies.

The characteristic fingerprint of conventional dairy Nanhanshuishi was established by X-ray diffraction (XRD), based on similarity of caculation on public peaks by MATLAB software, and the feasibility of new dairy technology of microwave method was explored between XRD and the dissolution rate in artificial simulation gastric juices. The result showed that similarity of shared peak in XRD of conventional dairy Nanhanshuishi was > 95%, This XRD characteristic fingerprint of conventional dairy Nanhanshuishi had strong specificity, could be used to provide a reference for identification and quality evaluation. This study also showed that the similarity of microware dairy products and conventional dairy products was good, and the sample of microwave 15 min was the best, and new dairy method by the microwave could replace the traditional method.

The large yellow croaker Larimichthys crocea (L. crocea) is one of the most economically important marine fish in China and East Asian countries. It also exhibits peculiar behavioral and physiological characteristics, especially sensitive to various environmental stresses, such as hypoxia and air exposure. These traits may render L. crocea a good model for investigating the response mechanisms to environmental stress. To understand the molecular and genetic mechanisms underlying the adaptation and response of L. crocea to environmental stress, we sequenced and assembled the genome of L. crocea using a bacterial artificial chromosome and whole-genome shotgun hierarchical strategy. The final genome assembly was 679 Mb, with a contig N50 of 63.11 kb and a scaffold N50 of 1.03 Mb, containing 25,401 protein-coding genes. Gene families underlying adaptive behaviours, such as vision-related crystallins, olfactory receptors, and auditory sense-related genes, were significantly expanded in the genome of L. crocea relative to those of other vertebrates. Transcriptome analyses of the hypoxia-exposed L. crocea brain revealed new aspects of neuro-endocrine-immune/metabolism regulatory networks that may help the fish to avoid cerebral inflammatory injury and maintain energy balance under hypoxia. Proteomics data demonstrate that skin mucus of the air-exposed L. crocea had a complex composition, with an unexpectedly high number of proteins (3,209), suggesting its multiple protective mechanisms involved in antioxidant functions, oxygen transport, immune defence, and osmotic and ionic regulation. Our results reveal the molecular and genetic basis of fish adaptation and response to hypoxia and air exposure. The data generated by this study will provide valuable resources for the genetic improvement of stress resistance and yield potential in L. crocea.

Percutaneous coronary intervention [PCI or percutaneous transluminal coronary angioplasty (PTCA)] has been developed into a mature interventional treatment for atherosclerotic cardiovascular disease. However, the long-term therapeutic effect is compromised by the high incidence of vascular restenosis following angioplasty, and the underlying mechanisms of vascular restenosis have not yet been fully elucidated. In the present study, we investigated the role of the gap junction (GJ) protein, connexin 43 (Cx43), in the development of vascular restenosis. To establish vascular restenosis, rat carotid arteries were subjected to balloon angioplasty injury. At 0, 7, 14 and 2 days following balloon injury, the arteries were removed, and the intimal/medial area of the vessels was measured to evaluate the degree of restenosis. We found that the intimal area gradually increased following balloon injury. Intimal hyperplasia and restenosis were particularly evident at 14 and 28 days after injury. In addition, the mRNA and protein expression of Cx43 was temporarily decreased at 7 days, and subsequently increased at 14 and 28 days following balloon injury, as shown by RT-PCR and western blot analysis. To determine the involvement of Cx43 in vascular restenosis, the lentivirus vector expressing shRNA targeting Cx43, Cx43-RNAi-LV, was used to silence Cx43 in the rat carotid arteries. The knockdown of Cx43 effectively attenuated the development of intimal hyperplasia and vascular restenosis following balloon injury. Thus, our data indicate the vital role of the GJ protein, Cx43, in the development of vascular restenosis, and provide new insight into the pathogenesis of vascular restenosis. Cx43 may prove to be a novel potential pharmacological target for the prevention of vascular restenosis following PCI.

Our previous study indicated that sulphur-fumigation of ginseng in post-harvest handling processes could induce chemical transformation of ginsenosides to generate multiple ginsenoside sulphur derivatives. In this study, the influence of sulphur-fumigation on intestinal metabolism and absorption in vivo of ginsenosides in ginseng was sequentially studied. The intestinal metabolic and absorbed profiles of ginsenosides in rats after intra-gastric (i.g.) administration of sulphur-fumigated ginseng (SFG) and non-fumigated ginseng (NFG) were comparatively characterized by a newly established ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) with electrospray ionization negative (ESI-) mode. A novel strategy based on the characteristic product ions and fragmentation pathways of different types of aglycones (saponin skeletons) and glycosyl moieties was proposed and successfully applied to rapid structural identification of ginsenoside sulphur derivatives and relevant metabolites. In total, 18 ginsenoside sulphur derivatives and 26 ginsenoside sulphur derivative metabolites in the faeces together with six ginsenoside sulphur derivatives in the plasma were identified in the SFG-administrated group but not in the NFG-administrated group. The results clearly demonstrated that the intestinal metabolic and absorbed profiles of ginsenosides in sulphur-fumigated and non-fumigated ginseng were quite different, which inspired that sulphur-fumigation of ginseng should not be recommended before the bioactivity and toxicity of the ginsenoside sulphur derivatives were systematically evaluated., (Copyright © 2014 John Wiley & Sons, Ltd.)

Objective: To study the effect and mechanism of soluble dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (sDC-SIGN) on the phagocytosis of Staphylococcus aureus (S. aureus) by immature dendritic cells (imDCs)., Methods: Flow cytometry was employed to examine the effect of sDC-SIGN on the phagocytosis of S. aureus by imDCs. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the binging of sDC-SIGN to S. aureus, lipoteichoic acid (LTA) and lipopolysaccharides (LPS) and investigate the effect of the ligands mannan and LTA and anti-DC-SIGN antibodies 1C6 and 4H3 on the binging of sDC-SIGN to S. aureus., Results: sDC-SIGN inhibited the phagocytosis of S. aureus by imDCs. sDC-SIGN bound to S. aureus in a Ca(2+)-dependent manner. sDC-SIGN concentration-dependently bound to LTA, but not to LTA, and the binging of sDC-SIGN to S. aureus was blocked by mannan, LTA, 1C6 and 4H3., Conclusion: sDC-SIGN preferentially binds to the carbohydrate constituents on S. aureus to affect the binding between membrane-bound DC-SIGN and S. aureus, thus suppressing the phagocytosis of S. aureus by imDCs.

Dendritic cells (DCs) are among the most important professional antigen-presenting cells (APCs) that participate in various biological activities in mammals. However, evidence of the existence of DCs in teleost fish and other lower vertebrates remains limited. In this study, phenotypic and functional characteristics of teleost DCs were described in a zebrafish model. An improved method to efficiently enrich DCs was established. Immunofluorescence staining revealed that the surface phenotypic hallmarks of mammalian DCs, including MHC-II, CD80/86, CD83, and CD209, were distributed on the surfaces of zebrafish DCs (DrDCs). Functional analysis results showed that DrDCs could initiate antigen-specific CD4(+) T cell activation, in which MHC-II, CD80/86, CD83, and CD209 are implicated. Hence, teleost DCs exhibit conserved immunophenotypes and functions similar to those of their mammalian counterparts. Our findings contributed to the current understanding of the evolutionary history of DCs and the DC-regulatory mechanisms of adaptive immunity., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Hainantoxin-IV (HNTX-IV) from the venom of the spider Selenocosmia hainana is a potent antagonist that specifically inhibits the tetrodotoxin-sensitive (TTX-S) sodium channels. The toxin peptide consists of 35 amino acids and adopts a typical inhibitory cystine knot (ICK) motif. To obtain adequate HNTX-IV peptides for further insight into the structure-activity relationships of the toxin, a novel strategy including cloning, expression and purification was developed in an E. coli expression system. For this purpose, a seamless restriction-free (RF) cloning method was employed for the construction of an expression vector to avoid introducing unwanted sequences into the target gene. Furthermore, the solubility of recombinant HNTX-IV could be promoted efficiently by the combination of a glutathione S-transferase (GST) tag and a small ubiquitin-related modifier (SUMO) tag. Finally, an affinity-chromatography-free purification strategy was developed by cut-off dialysis tubing combined with trichloroacetic acid (TCA) extraction. Further HPLC purification yielded recombinant, tag-free HNTX-IV with high yield and purity. The molecular weight of recombinant HNTX-IV (rHNTX-IV) is identical to its theoretical value according to Matrix-Assisted Laser Desorption / Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) analysis. The recombinant toxin has similar activity (IC50 value of 120 nM) on the tetrodotoxin-sensitive (TTX-S) sodium channels in adult rat dorsal root ganglion (DRG) neurons to native toxins. In the report, an efficient and cost-effective strategy for producing rHNTX-IV was developed, which paved the way for the further study of structure-activity relationships of rHNTX-IV and its pharmaceutical applications.

Objectives: To analyse the clinical features, inflammatory markers and radiographs of community-acquired pneumonia (CAP) cases with lobe or multi foci infiltration; with a special focus on factors which allow the differential diagnosis of viral and mycoplasma pneumonia., Setting: Retrospective chart review of CAP cases in a large university teaching hospital., Participants: 126 paediatric CAP cases, with lobe or multi foci infiltration, presenting between May 2012 and April 2013. Demographic data, clinical presentation on admission or referral, laboratory tests, prior history, and radiography were collected for each case if available., Primary and Secondary Outcome Measures: We used univariate and multivariate logistic regression to determine the significant factors which allow the differential diagnosis of viral and mycoplasma CAP with lobe or multi foci infiltration., Results: There were 71 (56%) male and 55 (44%) female CAP cases with lobar or multi foci infiltration. 70 pneumonia cases were caused by Mycoplasma pneumoniae and 18 by viruses. Univariate analysis of the mycoplasma and viral causes of the CAP revealed that increased respiratory rate, wheeze, male gender and lymphocyte percentage were the factors associated with the differentiation of mycoplasma and viral aetiologies of pneumonia (p<0.05). A stepwise logistic regression analysis was performed to assess independent factors which allow the differential diagnosis of viral and mycoplasma pneumonia. Increased respiratory rate, wheeze, and lymphocyte percentage were reliable independent factors which allow the differential diagnosis of viral and mycoplasma CAP with lobar or multi foci infiltration., Conclusions: Whether the CAP with lobar or multi foci infiltration was caused by mycoplasma species or viruses could not be inferred from the radiological patterns. Wheeze, lymphocyte percentage and respiratory rate were independent factors which allowed the differential diagnosis of viral and mycoplasma CAP with lobar or multi foci infiltration., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Context: Fetuin-A is an abundant plasma protein known to inhibit insulin signaling and pathologic calcification, has emerged as a promising candidate biomarker for diabetes risk., Objective: The objective of this study was to investigate the relationships between plasma Fetuin-A level with clinical characteristics in patients with new-onset type 2 diabetes mellitus (nT2DM)., Subjects and Methods: Plasma Fetuin-A levels, and clinical characteristics were assessed in 100 patients with nT2DM and 100 normal glucose tolerance (NGT)., Results: nT2DM subjects had significantly higher Fetuin-A levels than NGT subjects (368.5 ± 15.6 vs 152.7 ± 7.1 mg/ml, P < 0.01). In the Pearson's correlation coefficients, Fetuin-A levels and clinical parameters. Fetuin-A was positively correlated with HOMA-insulin resistance index (HOMA-IR), carotid intima media thickness(CIMT), HbA1c, triglyceride (TG), Low-density lipoprotein cholesterol (LDL-C), body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FBG) and 2 h post-glucose load blood glucose (2 h OGTT) (P < 0.05 and P < 0.01), but negatively with fasting plasma insulin (FINS), 2 h plasma insulin after glucose overload (PINS), High-density lipoprotein cholesterol (HDL-C) and HOMA-beta-cell insulin secretion index (HOMA-IS) (P < 0.05 and P < 0.01). However, no significant relationships were observed between plasma Fetuin-A levels and estimated glomerular filtration rate (eGFR), age and gender in nT2DM subjects. In a multiple linear regression analysis, Fetuin-A levels were independently associated with FBG, 2 h OGTT, HOMA-IS, TG, and CIMT (R(2) = 0.6760). CIMT were negatively associated with FINS and HDL-C (r = -0.33, P = 0.008; r = -0.31, P = 0.01, respectively) in the Pearson's analyses. Moreover, they were positively associated with HOMA-IR (r = 0.28, P = 0.03). It showed significant correlations of plasma CIMT with FINS, PINS and HOMA-IR (R(2) = 0.6760)., Conclusions: Our study suggests that the plasma Fetuin-A levels may be associated with macroangiopathies in nT2DM patients. Therefore, detecting early plasma Fetuin-A levels nT2DM provides an opportunity to intervene of carotid artery disease in diabetic patients and giving timely treatment for the prevention of diabetic vascular complications.

The classic Lossen rearrangement is a well-known reaction describing the transformation of an O-activated hydroxamic acid into the corresponding isocyanate. In this study, we found that chlorinated benzoquinones (CnBQ) serve as a new class of agents for the activation of benzohydroxamic acid (BHA), leading to Lossen rearrangement. Compared to the classic one, this new kind of CnBQ-activated Lossen rearrangement has the following unique characteristics: (1) The stability of CnBQ-activated BHA intermediates was found to depend not only on the degree but also on the position of Cl-substitution on CnBQs, which can be divided into two subgroups. (2) It is the relative energy of the anionic CnBQ-BHA intermediates that determine the rate of this CnBQ-activated rearrangement, which is the rate-limiting step, and the Cl or H ortho to the reaction site at CnBQ is crucial for the stability of the anionic intermediates. (3) A pKa-activation energy correlation was observed, which can explain why the correlation exists between the rate of the rearrangement and the acidity of the conjugate acid of the anionic leaving group, the hydroxlated quinones. These findings may have broad implications for future research on halogenated quinoid carcinogens and hydroxamate biomedical agents.

Objective: This study aims to investigate the number changes and the clinical significance of the peripheral blood T lymphocyte subsets and NK (natural killer) cells in unexplained recurrent spontaneous abortion (URSA) patients before and after abortion, as well as after successful pregnancy., Materials and Methods: Thirty-nine URSA patients (URSA-abortion group), among who 22 patients were followed up until the final successful parturition (URSA-pregnancy group), 31 normal-pregnancy (NP) cases and 25 normal non-pregnancy (NNP) control cases in which the peripheral blood T lymphocytes and subsets, B cells, and NK cells were assessed flow cytometry., Results: Compared with the URSA-pregnancy group and the NP group, the Th cells and NK cells of the URSA-abortion group increased (p < 0.05); compared with the NNP group, the total number of T cells decreased after the first, second, and third month of the URSA abortion (p < 0.05); Th cells decreased within one to six months of the URSA abortion (p < 0.05); proportion of NK cells was significantly higher in URSA patients (p < 0.05)., Conclusion: The abnormal numbers of the peripheral blood T cell subsets and NK cells were related with the occurrence of URSA.

This paper aims to explore head-to-toe deformation law for abdominal tumor with CTVision and selfdesigned respiratory movement simulation mold and meanwhile verify the accuracy and correctness of the treatment. In experimental group, a self-designed respiratory movement mold was used. The image was scanned out by CT scanning based on the movement state and then sent to the planning system to compare the location variation of tumor and formulating the treatment plan accordingly, followed by verification and verified derivation values observation. A total of 21 cases of abdominal tumor were included in the case group. Their breathing movement was detected under a simulated locator and then the data was recorded. The image was scanned and sent to the planning system to compare the location variation of the tumor, the patients then underwent 3D conformal therapy (3D-CRT) and we performed verification and observed verified derivation values. Finally, the results of the case group and the experimental group were compared. The mean of the verified derivation values was smaller than respiratory motion values in experimental group (t=-10.78, P=0, P < 0.05); the mean of verified derivation values of the patients was smaller than respiratory motion values in group f, g, h, i, j, l, n, o, p, q, r, s t, u in the case group (P < 0.05); no remarkable difference was found between the two values in group a, b, c, k and m (P < 0.05); group e was unable to undergo the statistical test since its standard deviation was 0; the mean of the verified derivation values was higher than respiratory motion values in group d (P < 0.05). In conclusion, radiation therapy applied with CTVision proved to be accurate and convincing in the treatment of abdominal tumor.

Objective: The interaction between advanced glycation end products and their cellular receptor (RAGE) has an important role in the pathogenesis of diabetic microvascular complications. The aim of this study was to investigate the relationship between the 2184A/G polymorphism in the RAGE gene and diabetic nephropathy in Chinese Han patients with type 2 diabetes mellitus., Methods: A total of 868 patients with type 2 diabetes mellitus (486 without and 382 with diabetic nephropathy) were enrolled in this study. The genotype and allele frequencies of the 2184A/G polymorphism were detected using the polymerase chain reaction-restriction fragment-length polymorphism method., Results: The G allele and AG + GG genotype frequencies in patients with diabetic nephropathy were significantly lower than those in patients without diabetic nephropathy (P = 0.001 and P = 0.005, resp.). After adjustments for possible confounders, multivariate logistic regression analyses showed that the 2184A/G polymorphism was independently associated with diabetic nephropathy (OR = 0.46, 95% CI: 0.22-0.92, P = 0.028)., Conclusions: Our study indicated that the 2184A/G polymorphism in the RAGE gene was significantly associated with diabetic nephropathy in Chinese Han patients with type 2 diabetes.

Background: Hepatocellular carcinoma (HCC) is one of the most important health problems in China., Objectives: This study analyzed expression of high-mobility group protein B1 (HMGB1) and inhibitor of apoptosis protein-2 (c-IAP2) proteins in HCC compared to paired para-tumor tissue samples to assess the association with HCC pathogenesis and progression., Materials and Methods: Sixty-eight HCC and para-tumor tissue samples were collected for Western blot, qRT-PCR and immunohistochemical analyses of HMGB1 and c-IAP2., Results: HMGB1 and c-IAP2 proteins were highly expressed in HCC tissue samples [85.3% (58/68) and 82.4% (56/68), respectively] compared to para-tumor tissue samples [32.3% and 27.9%, respectively]. Furthermore, expression of HMGB1 was significantly associated with enhanced c-IAP2 expression in HCC tissue samples (r = 0.878, P < 0.01). Expression of HMGB1 was associated with tumor multiplicity and size, alpha-fetoprotein (AFP) level and advanced TNM stage, while expression of c-IAP2 was associated with tumor size, AFP level and advanced TNM stage., Conclusions: Expression of HMGB1 and c-IAP2 proteins was associated with HCC development and progression, and the expression of HMGB1 and c-IAP2 proteins in HCC were significantly associated with each other. Additionally, these proteins may show promise as biomarkers to predict HCC progression.

Objective: The study aims to clarify the role of narrow band imaging (NBI) in the prediction of invasion depth and the formation of lesion appearance under NBI with immunohistochemical analysis., Materials and Methods: As a prospective single-center study, Sano's classification of capillary pattern (CP) was applied to differentiate early colorectal neoplasms under NBI observation. Only lesions with CP type III were analyzed, compared with final histologic findings, and further immunohistochemical analysis with CD34 and matrix metalloproteinase-7 (MMP-7) was performed., Results: As for the 203 cases of CP type III lesions, the sensitivity, specificity, and accuracy for CP type IIIA/IIIB were, respectively, 88.4, 93.6, and 92.5% to differentiate high-grade neoplasia or slight submucosal invasive carcinoma from deep submucosal invasive carcinoma. NBI prediction for invasion depth corresponded to immunohistochemical outcomes of CD34 and MMP-7, which might explain the reason why CP type IIIB displays nearly avascular or loose microvascular areas on the lesion surface., Conclusion: NBI is of excellent use in predicting invasion depth for early colorectal neoplasms, and positive expression of MMP-7 is associated with the appearance of CP type IIIB.

Objective: To evaluate the eradication rates, side effects and the patient compliance of a dual therapy with rabeprazole and amoxicillin as the first-line therapy in patients with Helicobacter pylori (H. pylori) infection., Methods: A total of 120 patients diagnosed endoscopically with non-ulcer dyspepsia with H. pylori infection were randomly assigned into two groups, one treated with amoxicillin 1 g thrice daily plus rabeprazole 10 mg twice daily (R10A group) or 20 mg twice daily (R20A group) for 14 days. H. pylori eradication was evaluated by (13) C-urea breath test (UBT) at 4-6 weeks after the completion of treatment. H. pylori eradication rate was analyzed by per-protocol (PP) and intention-to-treat (ITT) analyses together with 95% confidence interval (CI). Side effects and patients' compliance were also recorded., Results: Overall, 117 patients (58 in the R10A group and 59 in the R20A group) completed the study, among whom five did not undertake the UBT. H. pylori eradication was achieved in 89.8% of patients in the R20A group by ITT analysis and 93.0% by PP analysis, which was significantly higher than those in the R10A group (75.9% and 80.0%, respectively, P < 0.05). Side effects, including skin rash, abdominal discomfort, headache, insomnia and nausea, were all mild and were treated symptomatically without the need to discontinue the treatment., Conclusion: The modified dual therapy with high doses of rabeprazole and amoxicillin is considered an effective and safe primary therapy for H. pylori eradication and could be recommended as the first-line eradication regimen for certain patients., (© 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Fetuin-A, which is known to inhibit insulin signaling and pathological calcification, has emerged as a diabetes risk biomarker. In the present study, the association between the fetuin-A levels with insulin resistance (IR) and carotid intima-media thickness (CIMT) was investigated in patients with new-onset type 2 diabetes mellitus (nT2DM). A total of 100 patients with nT2DM (nT2DM group) and 100 normal glucose tolerance (NGT group) controls were evaluated. The serum fetuin-A level was measured by a commercial solid-phase ELISA kit. The estimate of IR was calculated by homeostasis model assessment (HOMA-IR). CIMT was measured by B-mode ultrasound. The association between the serum fetuin-A levels and the metabolic parameters was also analyzed. The serum fetuin-A levels were increased significantly in the nT2DM group compared to the NGT group (368.5±15.6 mg/ml vs. 152.7±7.1 mg/ml, P<0.01). Fetuin-A was positively correlated with HOMA-IR, CIMT, glycated hemoglobin, triglyceride, low-density lipoprotein cholesterol, body mass index, systolic blood pressure, fasting blood glucose and 2 h post-glucose load blood glucose (P<0.05 and P<0.01), but negatively correlated with fasting plasma insulin, 2 h plasma insulin after glucose overload, high-density lipoprotein cholesterol and HOMA-β-cell insulin secretion index (P<0.05 and P<0.01). To the best of our knowledge, the study demonstrated for the first time that there is a significant association between the serum fetuin-A levels with IR and CIMT in nT2DM. These results indicate that serum fetuin-A levels can be used as independent markers in the diagnosis of macroangiopathies in nT2DM.

The purpose of this study was to establish a method for measuring the knee valgus angle from the anatomical and mechanical axes on three-dimensional reconstruction imaging models, and to use this method for estimating an average knee valgus angle value for northern Chinese adults. Computed tomographic angiography data in DICOM format for 128 normal femurs from 64 adult subjects were chosen for analysis. After the femur images were subjected to three-dimensional reconstruction, the deepest point in the intercondylar notch (point A), the midpoint of the medullary cavity 20 cm above the knee-joint line (point B), and the landmark of the femoral head rotation center (point C) were identified on each three-dimensional model. The knee valgus angle was defined as the angle enclosed by the distal femoral anatomical axis (line AB) and the femoral mechanical axis (line AC). The average (mean±SD) of knee valgus angle for the 128 femurs was 6.20°±1.20° (range, 3.05° to 10.64°). Significant positive correlations were found between the knee valgus angles of the right and left sides and between the knee valgus angle and age. During total knee arthroplasty, choosing a valgus cut angle of approximately 6° may achieve a good result in reestablishing the natural mechanical alignment of the lower extremity for patients of northern Chinese ethnicity. Larger valgus cut angles should be chosen for older patients.

In present study, an ultra high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS) based metabolomics approach was established to investigate the metabolic profiles and characteristic chemical markers for distinguishing between leaves of Panax ginseng (LPG) and Panax quinquefolius (LPQ). The UHPLC-QTOF-MS/MS data were subjected to principal component analysis (PCA) and orthogonal partial least squared discrimination analysis (OPLS-DA) to rapidly find the potential characteristic components of LPG and LPQ, and the identities of detected peaks including the potential characteristic components were elucidated. Totally, 86 components were identified from these 2 kinds of leaf samples, in which 9 ginsenosides could be regarded as the characteristic chemical markers for the discrimination of LPG from LPQ. These results suggested that UHPLC-QTOF-MS/MS based metabolomics approach is a powerful tool to rapidly find characteristic markers for the quality control of LPG., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In the present study, we investigated the effects of Se-enriched Agaricus blazei Murill (Se-AbM) on liver injury in mice induced by acute alcohol administration. Mice received ethanol (5 g/kg body weight (BW)) by gavage every 12 h for a total of 3 doses. Se-AbM was administrated before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), nuclear factor kappa B (NF-κB) level, polymorphonuclear cells (PMN) level, interleukin-1β (IL-1β) level, inducible nitric oxide synthase (iNOS) level, tumor necrosis factor-α (TNF-α) level, intercellular adhesion molecule 1 (ICAM-1), and cyclooxygenase-2 (COX-2) were determined by ELISA and immunohistochemistry, respectively. Se-AbM administration markedly (p < 005) decreased serum ALT, AST, and MDA levels, hepatic IL-1β and TNF-α levels, as well as PMN infiltration and the expression of ICAM-1, COX-2, iNOS, and NF-κB compared with alcohol administration. In conclusion, we observed that Se-AbM supplementation could restrain the hepatic damage caused by acute alcohol exposure.

Chronic foot wounds are a leading cause of morbidity and hospitalization for patients with diabetes. Negative pressure wound therapy (NPWT) is known to promote healing of diabetic foot wounds, but the underlying molecular mechanisms remain elusive. We propose to gain molecular insights into the wound healing promoting signals underlying the effects of NPWT on diabetic foot wounds in humans. We assessed 30 patients with diabetic foot ulcers. Of these cases, 15 were treated with NPWT, while 15 patients were treated with traditional gauze therapy. Granulated tissue was harvested before and after treatment in both patient groups and histologically analyzed with hematoxylin & eosin as well as Masson's trichrome staining methods. Immunohistochemistry and Western blot analysis was performed to evaluate expression of basic fibroblast growth factor (bFGF) and extracellular signal-regulated kinase (ERK)1/2, previously associated with promoting cellular growth and/or wound healing. Unlike controls, the wounds in the NPWT-treated diabetic patients developed characteristic features of granulated tissue with increased collagen deposition. Immunohistochemical analysis also revealed an increase in bFGF levels in NPWT-treated patients. Western blot analysis further showed a significant up-regulation of bFGF and phosphorylated ERK1/2 protein levels in the NPWT-treated diabetic patients vs. controls. Our studies reveal that NPWT is associated with an up-regulation of bFGF and ERK1/2 signaling, which may be involved in promoting the NPWT-mediated wound healing response., (© 2014 by the Wound Healing Society.)

Narrow-band imaging (NBI) is an imaging technique for endoscopy using optical filters to narrow the bandwidth of spectral transmittance. Through this narrow spectrum, NBI contrasts surface structure and microvascular architecture of various lesions. In this article we focus on the application of NBI for early-stage neoplasia in the esophagus, stomach and colon with a three-step strategy of endoscopic diagnosis: (i) the detection of abnormality; (ii) the differentiation between non-neoplasia and neoplasia; and (iii) staging for tumor extension and depth of invasion.

The voltage-gated sodium channel (VGSC) interacting peptide is of special interest for both basic research and pharmaceutical purposes. In this study, we established a yeast-two-hybrid based strategy to detect the interaction(s) between neurotoxic peptide and the extracellular region of VGSC. Using a previously reported neurotoxin JZTX-III as a model molecule, we demonstrated that the interactions between JZTX-III and the extracellular regions of its target hNav1.5 are detectable and the detected interactions are directly related to its activity. We further applied this strategy to the screening of VGSC interacting peptides. Using the extracellular region of hNav1.5 as the bait, we identified a novel sodium channel inhibitor SSCM-1 from a random peptide library. This peptide selectively inhibits hNav1.5 currents in the whole-cell patch clamp assays. This strategy might be used for the large scale screening for target-specific interacting peptides of VGSCs or other ion channels.

Endometrial carcinoma (EC) is the most common gynecologic cancer worldwide and is one of the leading causes of death in women. Therefore, it is urgent to elucidate the pathological mechanisms of EC. SERPINA3 is a member of the serpin super-family of protease inhibitors. Its aberrant expression has been observed in various tumor cells. However, its clinical significance and biological function in endometrial cancer remains unknown. In the present study, we demonstrated that SERPINA3 expression was significantly up-regulated in EC samples and was closely correlated with lower differentiation, higher stage, positive lymph node or vascular thrombosis and negative estrogen receptor (ER), indicating a poor prognosis. We then demonstrated that SERPINA3 promoted EC cells proliferation by regulating G2/M checkpoint in cell cycle and inhibited cells apoptosis, and we further uncovered that the pro-proliferative effect of SERPINA3 on EC was likely ascribed to the activation of MAPK/ERK1/2 and PI3K/AKT signaling. The results of our study may provide insight into the application of SERPINA3 as a novel predictor of clinical outcomes and a potential therapeutic target of EC.

The long-held paradigm that B cells cannot uptake nonspecific particulate Ags for the initiation of primary adaptive immunity has been challenged by the recent discovery that teleost B cells have potent phagocytic and microbicidal abilities. This discovery provides preliminary clues that primitive B cells might act as initiating APCs in priming adaptive immunity. In this study, zebrafish B cells clearly showed a potent Ag-presenting ability to both soluble Ags and bacterial particles to prime naive CD4(+) T cell activation. This finding demonstrates the innate-like nature of teleost B cells in the interface of innate and adaptive immunity, indicating that they might consist of a major population of initiating APCs whose performance is similar to that of dendritic cells. Given the functional similarities between teleost B cells and the mammalian B-1 subset, we hypothesize that B-1 lineage and teleost B cells might originate from a common ancestor with potent phagocytic and initiating APC capacities. In addition, CD80/86 and CD83 costimulatory signals were identified as being essential for B cell-initiated adaptive immunity. This result suggests that the costimulatory mechanism originated as early as the origin of adaptive immunity and is conserved throughout vertebrate evolution. In fish, only a single CD80/86 copy exists, which is similar to mammalian CD86 rather than to CD80. Thus, CD86 might be a more primordial B7 family member that originated from fish. This study provides valuable insights into the evolutionary history of professional APCs, B cell lineages, and the costimulatory mechanism underlying adaptive immunity as a whole.

The suppressor of cytokine signaling 1 (SOCS-1) protein is a critical regulator in the immune systems of humans and mammals, which functions classically as an inhibitor of the IFN signaling pathways. However, data on functional characterisation of SOCS-1 in ancient vertebrates are limited. In this study, we report the function of teleost SOCS-1s in IFN signaling in fish models (zebrafish and Tetraodon) and human cells. Structurally, teleost SOCS-1s share conserved functional domains with their mammalian counterparts. Functionally, teleost SOCS-1s could be significantly induced upon stimulation with IFN stimulants and zebrafish IFNφ1. Overexpression of teleost SOCS-1s could dramatically suppress IFNφ1-induced Mx, Viperin and PKZ activation in zebrafish, and IFN-induced ISG15 activation in HeLa cells. Furthermore, a SOCS-1 variant that lacks the KIR domain was also characterised. This study demonstrates the conserved negative regulatory role of teleost SOCS-1s in IFN signaling pathways, providing perspective into the functional conservation of SOCS-1 proteins during evolution., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The bioactivities, chemical composition and distribution of aerial parts of Panax species are different from the roots. The present paper summarized the phytochemical and analytical studies of aerial parts of Panax species, including P. ginseng, P. notoginseng, P. quinquefoliun and P. japonicus. This review aims so as to provide scientific evidences for further investigation of chemical profile, quality control and optimal utilization of these resources.

A high performance liquid chromatography-photodiode array detector (HPLC-PDA) fingerprinting and ultra high performance liquid chromatography-photodiode array detector coupled with quadrupole time-of-flight mass spectrometry (UHPLC-PDA-QTOF-MS/MS) based chemical profiling approach was developed to rapidly find characteristic chemical markers for quality control of dispensing granules, taking Chuanxiong Rhizoma (CR) as a model herb. Firstly, CR crude drugs, their traditional decoctions and CR dispensing granules were analyzed by HPLC-PDA to rapidly establish the fingerprints and thereby generate the simulative median chromatograms of CR crude drugs, decoctions and dispensing granules, and by comparing the simulative median chromatograms, major characteristic peaks of CR decoctions and dispensing granules could be determined. Secondary, UHPLC-PDA-QTOF-MS/MS was used to identify the major characteristic peaks of CR decoctions and dispensing granules. The identities of three major peaks were elucidated and confirmed to be ferulic acid (1), senkyunolide I (2) and senkyunolide H (3) by comparing the mass/UV spectra and retention times with that of the reference compounds. Thirdly, an HPLC-PDA method was validated to quantify the three characteristic components in commercial CR dispensing granules. The average contents of ferulic acid and senkyunolide H were found to be less than 1.0mg/g, whereas that of senkyunolide I was 4.40mg/g in CR dispensing granules, which indicated that senkyunolide I might be chosen as a suitable quantitative marker, while ferulic acid and senkyunolide H as qualitative markers for the quality evaluation of CR dispensing granules. It is suggested that this newly established approach could be used to practically and rapidly find suitable marker compounds for quality control of dispensing granules derived from other medicinal herbs., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To explore the role of Dlx1as, a natural antisense transcript, in mice brain development., Methods: Based on the bioinformatic and molecular biological findings, we confirmed whether the Dlx1as has a poly-A tail. The temporal expressions of Dlx1as and Dlx1 mRNA were determined by quantitative real-time PCR and the spatial expressions of Dlx1as and Dlx1 mRNA were compared by using in situ hybridization., Results: Dlx1as had a poly-A signal. Dlx1as's expression was at a high level through a period of time in the embryo development, which was similar with Dlx1 mRNA in temporal but different in spatial., Conclusions: Dlx1as is highly expressed in a certain period during mice brain development, which spatially supplements the mRNA expression of D1x1. Therefore, it is supposed that Dlx1as influences the mice brain development by regulating Dlx1 mRNA.

Tumor-associated macrophages (TAMs) constitute a major component of the leukocyte infiltrate of most solid tumors, and they usually exhibit a proangiogenic phenotype which facilitates tumor growth in most circumstances. However, the precise mechanisms regulating the proangiogenic properties of TAMs remain largely unclear. In the present study, we found that the expression of hypoxia-inducible factor 2α (HIF-2α) was significantly up-regulated in macrophages from tumor tissues of several solid tumors. Macrophages exposed to tumor cell line derived-culture supernatants (TSN) also expressed high levels of HIF-2α in vitro, without a requirement for hypoxia. We identified miR-17 and miR-20a as the key regulators of HIF-2α expression in TAMs, and autocrine IL-6 played an important role in mediating the expression of miR-17, miR-20a, and thereafter HIF-2α in TAMs. Furthermore, the elevated HIF-2α in TAMs stimulated transcription of a set of proangiogenic genes such as VEGFA and PDGFB, which might in turn contribute to the angiogenic process within tumors. Our data provide evidence in support of the critical role of HIF-2α in the proangiogenic activity of TAMs and also reveal a novel mechanism by which miRNAs regulate TAM functions through modulation of HIF-2α expression under non-hypoxic conditions.

Qiong-Yu-Gao (QYG), consisting of Rehmanniae Radix (RR), Poriae (PO) and Ginseng Radix (GR), is a commonly used tonic traditional complex herbal medicine (CHM). So far, three different methods have been documented for preparation of QYG, i.e. method 1 (M1): mixing powders of GR and PO with decoction of RR; method 2 (M2): combining the decoction of RR and PO with the decoction of GR; method 3 (M3): decocting the mixture of RR, GR and PO. In present study, an ultra-high performance liquid chromatography coupled with photo-diode array and quadrupole/time-of-flight mass spectrometry (UHPLC-PDA-QTOF-MS/MS) based chemical profiling approach was developed to investigate the influence of the three preparation methods on the holistic quality of QYG. All detected peaks were unambiguously identified by comparing UV spectra, accurate mass data/characteristic mass fragments and retention times with those of reference compounds, and/or tentatively assigned by matching empirical molecular formula with that of known compounds, and/or elucidating quasi-molecular ions and fragment ions referring to information available in literature. A total of 103 components, mainly belonging to ginsenosides, phenethylalcohol glycosides, iridoid glycosides and triterpenoid acids, were identified, of which 5 degraded ginsenosides were putatively determined to be newly generated during preparation procedures of QYG samples. Triterpenoid acids and malonyl-ginsenosides were detected only in M1 samples, while degraded ginsenosides were merely detectable in M2/M3 samples. The possible reasons for the difference among chemical profiles of QYG samples prepared with three methods were also discussed. It could be concluded that preparation method do significantly affect the holistic quality of QYG. The influence of the altered chemical profiles on the bioactivity of QYG needs further investigation. The present study demonstrated that UHPLC-PDA-QTOF-MS/MS based chemical profiling approach is efficient and reliable for evaluating the holistic quality of traditional CHM., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To investigate the risk factors of prostate cancer in urban Qingdao and provide some theoretical evidence for the scientific prevention and treatment of the disease., Methods: We performed a hospital-based matched case-control study in Qingdao Municipal Hospital. The cases and controls were matched in age, gender, nationality and the place of residence. All the subjects were interviewed face to face in the hospital using a questionnaire, and the data analyzed by the conditional logistic regression method., Results: According to the 258 valid questionnaires collected, the prostate cancer risk was significantly higher in the cases with a family history of cancer than in those without (OR = 2.58), and so was it in the men with the first spermatorrhea at the age of < or = 15 years than in those at the age of > or = 18 years (OR = 2.27). A decreased risk of prostate cancer was found among the men with the first experience of sexual intercourse between 25 to 30 years of age (OR = 0.76). An increased risk was shown in those with sexual intercourses > or = 4 times per week before 35 years old (OR = 2.57), masturbations > or = 3 times per week (OR = 2.30) and a drinking history (alcohol > or = 150 g/d) of > or = 10 years (OR = 2.83)., Conclusion: Positive family history of cancer, earlier age of the first spermatorrhea, sexual intercourses > or = 4 times per week before 35 years old, frequent masturbations, and heavy drinking for more than 10 years are risk factors for prostate cancer.

We report a study of ν(μ) charged-current quasielastic events in the segmented scintillator inner tracker of the MINERvA experiment running in the NuMI neutrino beam at Fermilab. The events were selected by requiring a μ- and low calorimetric recoil energy separated from the interaction vertex. We measure the flux-averaged differential cross section, dσ/dQ², and study the low energy particle content of the final state. Deviations are found between the measured dσ/dQ² and the expectations of a model of independent nucleons in a relativistic Fermi gas. We also observe an excess of energy near the vertex consistent with multiple protons in the final state.

We have isolated ν(μ) charged-current quasielastic (QE) interactions occurring in the segmented scintillator tracking region of the MINERvA detector running in the NuMI neutrino beam at Fermilab. We measure the flux-averaged differential cross section, dσ/dQ², and compare to several theoretical models of QE scattering. Good agreement is obtained with a model where the nucleon axial mass, M(A), is set to 0.99 GeV/c² but the nucleon vector form factors are modified to account for the observed enhancement, relative to the free nucleon case, of the cross section for the exchange of transversely polarized photons in electron-nucleus scattering. Our data at higher Q² favor this interpretation over an alternative in which the axial mass is increased.

Epimedium sagittatum (Sieb. et Zucc) Maxim is a member of the Berberidaceae family of basal eudicot plants, widely distributed and used as a traditional medicinal plant in China for therapeutic effects on many diseases with a long history. Recent data shows that E. sagittatum has a relatively large genome, with a haploid genome size of ~4496 Mbp, divided into a small number of only 12 diploid chromosomes (2n = 2x = 12). However, little is known about Epimedium genome structure and composition. Here we present the analysis of 691 kb of high-quality genomic sequence derived from 672 randomly selected plasmid clones of E. sagittatum genomic DNA, representing ~0.0154% of the genome. The sampled sequences comprised at least 78.41% repetitive DNA elements and 2.51% confirmed annotated gene sequences, with a total GC% content of 39%. Retrotransposons represented the major class of transposable element (TE) repeats identified (65.37% of all TE repeats), particularly LTR (Long Terminal Repeat) retrotransposons (52.27% of all TE repeats). Chromosome analysis and Fluorescence in situ Hybridization of Gypsy-Ty3 retrotransposons were performed to survey the E. sagittatum genome at the cytological level. Our data provide the first insights into the composition and structure of the E. sagittatum genome, and will facilitate the functional genomic analysis of this valuable medicinal plant.

Background: A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine., Methods: We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6-35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247., Findings: 10,245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1-96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2-90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33)., Interpretation: EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity., Funding: China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To investigate the effect of tea polyphenols on the proliferation of human prostate cancer cells and its possible mechanism., Methods: We cultured androgen-independent prostate cancer DU145 cells in the medium with different concentrations (50, 100, 250 and 500 microg/ml) of tea polyphenols, and those in the normal medium as the control. After 48 hours of culture, we detected the survival rate of the cells by MTT assay and determined the expression of survivin by Western blot and quantitative RT-PCR., Results: At 48 hours, the survival rates of the prostate cancer DU145 cells were 0.97 +/- 0.12, 0.71 +/- 0.07, 0.20 +/- 0.03 and 0.08 +/- 0.01 in the 50, 100, 250 and 500 microg/ml tea polyphenols treatment groups, all significantly reduced as compared with the control group (P < 0.01) except that of the 50 microg/ml group (P = 0.42). Furthermore, the survival rate continued to decrease with the prolonging of time, dropping below 5% at 96 hours except in the 50 microg/ml group. The grey values of the survivin expression in the 100, 250 and 500 microg/ml tea polyphenols groups were 13 425 +/- 34, 2 017 +/- 24 and 1 274 +/- 22, respectively, at 48 hours, significantly lower than 15 075 +/- 48 in the control group (P < 0.01). Moreover, the content of survivin mRNA at 48 hours was markedly lower in the 50, 100, 250 and 500 microg/ml treatment groups (0.74 +/- 0.03, 0.64 +/- 0.02, 0.52 +/- 0.01 and 0.21 +/- 0.02) than in the control (P < 0.01)., Conclusion: Tea polyphenols can inhibit the proliferation of human prostate cancer DU145 cells, which may be associated with the decreased expression of the survivin gene.

To describe the unique miRNA profiles for HIV seropositive individuals and identify significantly differently expressed miRNAs, we determined the expression level of 754 miRNAs of 10 HIV seropositive individuals and 10 HIV seronegative individuals by using the Taqman low density microRNA array. BRB-Array Tool was used to conduct the significance analysis, and the DIANA online tool was used to perform the miRNA target prediction and pathway analysis. A total of 56 significantly differentially expressed miRNAs were identified by microarray between HIV seropositive and seronegative individuals. Among them, 49 miRNAs were down-regulated and 7 were up-regulated, partially overlapped with reported data. Predicted target genes were mainly involved in MAPK, TGF-beta and Wnt pathways. The results shows that miRNA profile changes in HIV-1 seropositive individuals, and the 56 differentially expressed miRNAs may play important role during HIV infection. Further studies on these miRNAs may be helpful for identify key molecules involved in HIV infection and potential diagnostic markers.

Glycyrrhizae Radix (GR) is often prescribed together with Aconiti Laterlis Radix (ALR) (a so-called compatible drug pair) in traditional Chinese medicinal practice to reduce toxicity of ALR. However, the mechanisms involved remain to be addressed. In this study, the metabolic interactions between GR-ALR drug pair were investigated for the first time. First, an HPLC-TQ-MS/MS method was developed to analyze hypaconitine, a major bioactive and toxic component of ALR, in rat liver S9. Then the in vitro metabolic rates of hypaconitine by different rat liver S9 were compared using the established method. The experiments were designed in four groups: pure hypaconitine (group I) and ALR extract (group II) incubated with liver S9 of normal rats, and pure hypaconitine (group III) and ALR extract (group IV) incubated with liver S9 of GR-pretreated rats. When incubated for more than 4 h, the metabolic rates of hypaconitine in group III were significantly higher than those in group I, and when incubated for more than 2 h, the metabolic rates of hypaconitine in group IV were significantly higher than those in group II, suggesting that GR can enhance metabolic rate of hypaconitine, the mechanism of which might be related to hepatic metabolizing enzyme induction by GR., (Copyright © 2012 John Wiley & Sons, Ltd.)

Objective: Endoscopic resection (ER) was introduced to China from Japan, while most pathologists are influenced by Western criteria. Japanese and Western pathologists have debated for decades how best to distinguish between gastric intraepithelial neoplasia (GIEN) and early gastric cancer (EGC). In this study we aimed to find out how to solve this pathological discrepancy and improve the curative resection of lesions based on our experiences., Methods: In total, 143 patients with GIEN or EGC were treated by ER in our hospital from April 2008 to April 2012. The risk factors related to the degree of malignancy of the lesions and the non-curability of ER were analyzed. Pathological discrepancy between forceps biopsies and ER specimens was also compared., Results: According to the histological types of the ER specimens, there were 67 patients with low-grade intraepithelial neoplasia (LGIN), 35 with high-grade intraepithelial neoplasia (HGIN) and 41 with EGC. The ER histological type was significantly correlated with gender, ER method, macroscopic type, tumor size, ulcer and histological type of the forceps biopsy (P < 0.05). The discrepancy between forceps biopsy and ER specimens was 41.3% (59/143). Furthermore, the depth of tumor invasion and ER histological type were associated with the curative resection of HGIN and EGC (P < 0.05)., Conclusions: The pathological discrepancy shows that patients with HGIN in forceps biopsy should be considered candidates for ER. The risk factors of lesion malignancy and ER curability indicate the great importance of pretreatment evaluation for ER., (© 2013 The Authors. Journal of Digestive Diseases © 2013 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Magnetization noncollinearity in ferromagnet-superconductor (F/S) heterostructures is expected to enhance the superconducting transition temperature (T(c)) according to the domain-wall superconductivity theory, or to suppress T(c) when spin-triplet Cooper pairs are explicitly considered. We study the proximity effect in F/S structures where the F layer is a Sm-Co/Py exchange-spring bilayer and the S layer is Nb. The exchange-spring contains a single, controllable and quantifiable domain wall in the Py layer. We observe an enhancement of superconductivity that is nonmonotonic as the Py domain wall is increasingly twisted via rotating a magnetic field, different from theoretical predictions. We have excluded magnetic fields and vortex motion as the source of the nonmonotonic behavior. This unanticipated proximity behavior suggests that new physics is yet to be captured in the theoretical treatments of F/S systems containing noncollinear magnetization.