Alteromonas arenosi sp. nov., a novel bioflocculant-producing bacterium, isolated from intertidal sand.

A novel Gram-stain-negative, strictly aerobic and bioflocculant-producing bacterium, designated as ASW11-36T, was isolated from an intertidal sand collected from coastal areas of Qingdao, PR China. Growth occurred at 15-40 °C (optimum, 30 °C), pH 7.0-9.0 (optimum, pH 7.5) and with 1.5-7.0% (w/v) NaCl (optimum, 2.5-3.0%). In the whole-cell fatty acid pattern prevailed C16:0 and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). The major isoprenoid quinone was determined to be Q-8 and the major polar lipids were phosphatidylethanolamine (PE) and phosphatidylglycerol (PG), one unidentified aminolipid (AL), one unidentified glycolipid (GL), and two lipids (L1, L2). Based on the phylogenetic analyses of 16S rRNA gene sequences and 618 single-copy orthologous clusters, strain ASW11-36T could represent a novel member of the genus Alteromonas and was closely related to Alteromonas flava P0211T (98.4%) and Alteromonas facilis P0213T (98.3%). The pairwise average nucleotide identity and digital DNA-DNA hybridization values of the ASW11-36T genome assembly against the closely related species genomes were 71.8% and 21.7%, respectively, that clearly lower than the proposed thresholds for species. Based on phenotypic, phylogenetic, and chemotaxonomic analyses, strain ASW11-36T is considered to represent a novel species of the genus Alteromonas, for which the name Alteromonas arenosi sp. nov. is proposed. The type strain is ASW11-36T (= KCTC 82496T = MCCC 1K05585T). In addition, the strain yielded 65% of flocculating efficiency in kaolin suspension with CaCl2 addition. The draft genome of ASW11-36T shared abundant putative CAZy family related genes, especially involved in the biosynthesis of exopolysaccharides, implying its potential environmental and biological applications.

A Novel Polysaccharide Separated from Panax Notoginseng Residue Ameliorates Restraint Stress- and Lipopolysaccharide-induced Enteritis in Mice.

Polysaccharides are rich in Panax notoginseng residue after extraction. This study aims to explore the structural characteristics of PNP-20, which is a homogeneous polysaccharide, separated from P. notoginseng residue by fractional precipitation and evaluate the anti-enteritis effect of PNP-20. The structure of PNP-20 was determined by spectroscopic analyses. A mouse model with enteritis induced by restraint stress (RS) and lipopolysaccharide (LPS) was used to evaluate the pharmacological effect of PNP-20. The results indicated that PNP-20 consisted of glucose (Glc), galactose (Gal), Mannose (Man) and Rhamnose (Rha). PNP-20 was composed of Glcp-(1→, →4)-α-Glcp-(1→, →4)-α-Galp-(1→, →4,6)-α-Glcp-(1→, →4)-Manp-(1→ and →3)-Rhap-(1→, and contained two backbone fragments of →4)-α-Glcp-(1→4)- α-Glcp-(1→ and →4)-α-Galp-(1→4)-α-Glcp-(1→. PNP-20 reduced intestinal injury and inflammatory cell infiltration in RS- and LPS-induced enteritis in mice. PNP-20 decreased the expression of intestinal tumor necrosis factor-α, NOD-like receptor family pyrin domain containing 3, and nuclear factor-κB and increased the expression of intestinal superoxide dismutase 2. In conclusion, PNP-20 may be a promising material basis of P. Notoginseng for the treatment of inflammatory bowel disease.

Identification of GnRH-like peptide and its potential signaling pathway involved in the oocyte meiotic maturation in the Chinese mitten crab, Eriocheir sinensis.

Gonadotropin-releasing hormone (GnRH) plays a pivotal role in reproductive regulation in vertebrates. However, GnRH was rarely isolated and its function remains poorly characterized in invertebrates. The existence of GnRH in ecdysozoa has been controversial for a long. Here, we isolated and identified two GnRH-like peptides from brain tissues in Eriocheir sinensis. Immunolocalization showed that the presence of EsGnRH-like peptide in brain, ovary and hepatopancreas. Synthetic EsGnRH-like peptides can induce germinal vesicle breakdown (GVBD) of oocyte. Similar to vertebrates, ovarian transcriptomic analysis revealed a GnRH signaling pathway in the crab, in which most genes exhibited dramatically high expression at GVBD. RNAi knockdown of EsGnRHR suppressed the expression of most genes in the pathway. Co-transfection of the expression plasmid for EsGnRHR with reporter plasmid bearing CRE-luc or SRE-luc response element into 293T cells showed that EsGnRHR transduces its signal via cAMP and Ca2+ signaling transduction pathways. In vitro incubation of the crab oocyte with EsGnRH-like peptide confirmed the cAMP-PKA cascade and Ca2+ mobilization signaling cascade but lack of a PKC cascade. Our data present the first direct evidence of the existence of GnRH-like peptides in the crab and demonstrated its conserved role in the oocyte meiotic maturation as a primitive neurohormone.

Screening of Lymphoma Radiotherapy-Resistant Genes with CRISPR Activation Library.

Objective: The objective of this study was to screen lymphoma radiotherapy-resistant genes using CRISPR activation (CRISPRa). Methods: The Human CRISPRa library virus was packaged and then transfected into lymphoma cells to construct an activation library cell line, which was irradiated at the minimum lethal radiation dose to screen radiotherapy-resistant cells. Radiotherapy-resistant cell single-guide RNA (sgRNA) was first amplified by quantitative polymerase chain reaction (qPCR) in the coding region and then subject to next-generation sequencing (NGS) and bioinformatics analysis to screen radiotherapy-resistant genes. Certain radiotherapy-resistant genes were then selected to construct activated cell lines transfected with a single gene so as to further verify the relationship between gene expression and radiotherapy resistance. Results: A total of 16 radiotherapy-resistant genes, namely, C20orf203, MTFR1, TAF1L, MYADM, NIPSNAP1, ZUP1, RASL11A, PSMB2, PSMA6, OR8H3, TMSB4Y, CD300LF, EEF1A1, ATP6AP1L, TRAF3IP2, and SNRNP35, were screened based on the NGS results and bioinformatics analysis of the radiotherapy-resistant cells. Activated cell lines transfected with a single gene were constructed using 10 radiotherapy-resistant genes. The qPCR findings showed that, when compared with the control group, the experimental group had significantly up-regulated mRNA expression of MTFR1, NIPSNAP1, ZUP1, PSMB2, PSMA6, EEF1A1, TMSB4Y and TAF1L (p < 0.05). No significant difference in the mRNA expression of AKT3 or TRAF3IP2 (p > 0.05) was found between the two groups (p > 0.05). Conclusion: The 16 genes screened are potential lymphoma radiotherapy-resistant genes. It was initially determined that the high expression of 8 genes was associated with lymphoma radiotherapy resistance, and these genes could serve as the potential biomarkers for predicting lymphoma radiotherapy resistance or as new targets for therapy.

Design, synthesis and biological evaluation of cajanonic acid A analogues as potent PPAR γ antagonists.

Peroxisome proliferator-activated receptor γ (PPAR γ) antagonists are a key instrument of insulin sensitizers since they have the ability to sensitize insulin and can avoid adverse reactions caused by receptor agonist. In this paper, two series of 28 novel Cajanonic acid A (CAA) derivatives were designed and synthesized. The biological activity showed that a novel CAA derivative 9f was identified as a potential PPAR γ antagonist by medicinal chemistry efforts. The results in vitro displayed that compound 9f could improve the PPAR γ antagonist activity (96.2 % / 50.2 % decrease in PPAR γ transactivation at 10 µM / 1 µM, respectively). It also could improve the glucose consumption activity of insulin-resistant HepG2/3T3-L1 cell line (33.27 % / 72.61 % increase in glucose consumption). And in 3 T3-L1 adipocytes, it showed anti-adipogenesis activity (7.04 % increase in oil red staining). Further, in vivo study suggested that compound 9f could improve the oral glucose tolerance in db/db mice. Taken together, derivative 9f served as a promising candidate for anti-diabetic drug discovery and deserve further study.

Application of Multiparametric Magnetic Resonance Imaging to Monitor the Early Antitumor Effect of CuS@GOD Nanoparticles in a 4 T1 Breast Cancer Xenograft Model.

BACKGROUND: We have developed hybrid nanoparticles (NPs) by co-loading copper sulfide (CuS) NPs and glucose oxidase (GOD) (CuS@GOD NPs) to explore their antitumor properties. PURPOSE: To investigate the feasibility of using multiparametric magnetic resonance imaging (MRI) including intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and R2 * mapping to quantitatively assess the early antitumor effect of CuS@GOD NPs. STUDY TYPE: Prospective. ANIMAL MODEL: The orthotopic BALB/c mice 4 T1 breast cancer model. The 4 T1 xenografts in group 1 mice received normal saline, group 2 received CuS@GOD NPs, group 3 received CuS NPs plus laser, and group 4 received CuS@GOD NPs plus laser (n = 28 for each group). FIELD STRENGTH/SEQUENCE: A 3.0 T/IVIM-DWI MRI single-shot echo-planar imaging, R2 * mapping spoiled gradient recalled echo (SPGR) sequence, T2-weighted images (T2WI) and T1-weighted images (T1WI) fast spin echo (FSE) sequence. ASSESSMENT: The IVIM-DWI and R2 * mapping were performed before and after treatment at 0 hour, 0.5 hour, 1 hour, 2 hours, 4 hours, and 24 hours in four groups and the MRI parameters were obtained. Correlation analysis between the MRI parameters and histological analyses was conducted. STATISTICAL TESTS: One-way ANOVA, Pearson's correlation analysis, two independent samples t test, intraclass correlation coefficient. P < 0.05 was considered to be statistically significant. RESULTS: In group 4, the tumoral D value was significantly higher than that of group 2 at 24 hours (0.541 ± 0.065 vs. 0.492 ± 0.051). The f value of group 4 was significantly lower than that of groups 1 and 2 at 2 hours (10.83 ± 2.16 vs. 14.28 ± 1.86, 16.67 ± 3.53, respectively). The R2 * value was significantly increased at 0 hour in group 4 compared to that of groups 1 and 2 (64.552 ± 4.663 vs. 42.441 ± 1.516, 43.165 ± 1.709, respectively). D, f, and R2 * were correlated with the histological staining results (r = 0.695-0.970). DATA CONCLUSION: The IVIM-DWI-derived D and f and R2 * mapping-derived R2 * could monitor early response to CuS@GOD NPs treatment in vivo. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

A simple and feasible atom-precise biotinylated Cu(i) complex for tumor-targeted chemodynamic therapy.

A simple and feasible atom-precise biotinylated Cu(i) complex, which can catalyze H2O2 overexpressed commonly in the tumor microenvironment to produce ˙OH through a Fenton-like reaction, was prepared and employed as an effective agent for tumor-targeted chemodynamic therapy.

Evidences for Red Pigment Concentrating Hormone (RPCH) and Beta-Pigment Dispersing Hormone (ß-PDH) Inducing Oocyte Meiotic Maturation in the Chinese Mitten Crab, Eriocheir sinensis.

Red pigment concentrating hormone (RPCH) and pigment dispersing hormone (PDH) are crustacean neuropeptides involved in broad physiological processes including body color changes, circadian rhythm, and ovarian growth. In this study, the full-length cDNA of RPCH and PDH were identified from the brain of the Chinese mitten crab Eriocheir sinensis. The deduced RPCH and PDH mature peptides shared identical sequence to the adipokinetic hormone/RPCH peptides family and the ß-PDH isoforms and were designated as Es-RPCH and Es-ß-PDH, respectively. Es-RPCH and Es-ß-PDH transcripts were distributed in the brain and eyestalks. The positive signals of Es-RPCH and Es-ß-PDH were localized in the neuronal clusters 6, 8, 9, 10, and 17 of the brain as revealed by in situ hybridization. The expression level of Es-RPCH and Es-ß-PDH mRNA in nervous tissues were all significantly increased at vitellogenic stage, and then decreased at the final meiotic maturation stage. The administrated with synthesized Es-RPCH peptide results in germinal vesicles shift toward the plasma membrane in vitellogenic oocyte, and significant decrease of the gonad-somatic index (GSI) and mean oocyte diameter as well as the expression of vitellogenin mRNA at 30 days post injection in vivo. Similar results were also found when injection of the Es-ß-PDH peptide. In vitro culture demonstrated that Es-RPCH and Es-ß-PDH induced germinal vesicle breakdown of the late vitellogenic oocytes. Comparative ovarian transcriptome analysis indicated that some reproduction/meiosis-related genes such as cdc2 kinase, cyclin B, 5-HT-R and retinoid-X receptor were significantly upregulated in response to Es-RPCH and Es-ß-PDH treatments. Taken together, these results provided the evidence for the inductive effect of Es-RPCH and Es-ß-PDH on the oocyte meiotic maturation in E. sinensis.

Informal caregiver burden and influencing factors in gynaecological oncology patients hospitalized for chemotherapy: a cross-sectional study.

OBJECTIVE: To determine the level and influencing factors of informal caregiver burden in gynaecological oncology inpatients receiving chemotherapy. METHODS: This cross-sectional study enrolled gynaecological oncology patients and their informal caregivers between May 2018 and November 2018 and measured the caregivers' burden using the Caregiver Burden Inventory. The influencing factors were evaluated with univariate regression analysis and multivariate linear stepwise regression analysis. RESULTS: A total of 138 patients and their informal caregivers completed the questionnaire. The mean ± SD total informal caregiver burden score was 53.18 ± 10.97. The highest mean ± SD score was recorded in the dimension of time-dependent burden (14.28 ± 2.74), followed by developmental burden (13.65 ± 2.15), physical burden (10.52 ± 2.07), social burden (7.61 ± 2.58) and emotional burden (7.12 ± 1.43). Multivariate analysis showed that the informal caregiver's sex, relationship to the patient, daily duration of care, presence of chronic health problems and the duration of the patient's disease were factors influencing the level of caregiver burden. CONCLUSIONS: The informal caregivers of gynaecological cancer patients hospitalized for chemotherapy experience a moderate level of burden. Nursing measures should be considered to reduce informal caregiver burden and improve the quality of lives of both patients and their caregivers.

Two groups of copperII pyridine-triazole complexes with "open or close" pepper rings and their in vitro antitumor activities.

Based on 1,2-dimethoxyphenyl (veratrole, open) and 1,2-methylenedioxyphenyl (pepper ring, close)-derived pyridine-triazole analogues, two groups of copper(ii) complexes, namely, Group I(C1-C3) and Group II(C4-C6) were synthesized and fully characterized. All ligands and complexes were tested in vitro by MTT assays on seven tumour cell lines (T24, Hep-G2, Sk-Ov-3, MGC-803, HeLa, A549 and NCI-H460) and one normal liver cell line (HL-7702). Surprisingly, the pepper-ring-derived complexes (C4-C6) showed significantly enhanced cytotoxicity compared with the 1,2-bimethoxyphenyl ring-derived complexes (C1-C3) and the standard anticancer drug cisplatin. Cellular uptake assays indicated that the Cu accumulation was consistent with cytotoxicity. In addition, flow cytometry and western blot analysis showed that the apoptosis of the leading complex C4 may be induced by the Bcl-2 family-mediated proteins through the mitochondrial dysfunction pathway. Furthermore, UV-vis and fluorescence spectroscopy assays revealed that C4 has stronger insertion-binding interactions with CT-DNA than C1 and the fluorescence of C1 and C4 with BSA is mainly quenched by static quenching.

The effect of ghrelin O-acyltransferase inhibitor on gastric H+-K+-ATPase activity and GOAT/ghrelin system in gastric mucosal cells in vitro.

Ghrelin is implicated in the regulation of gastric functional development. The octanoylation of ghrelin is critical for its physiological functions which dependent upon ghrelin O-acyltransferase (GOAT) catalyzation. To investigate the effect of GOAT on gastric acid secretion and expression of ghrelin in vitro. Primary cultures of gastric mucosal cells were challenged with 1.5 × 10-5, 1.5 × 10-4 and 1.5 × 10-3 mol/mL GO-CoA-Tat (The GOAT inhibitor), respectively, for 24 h in order to further clarify the effect of GOAT on H+-K+-ATPase activity. In vitro, GO-CoA-Tat significantly increased ghrelin and GOAT mRNA expression at 1.5 × 10-5, 1.5 × 10-4 and 1.5 × 10-3 mol/mL, and augmented cell total ghrelin secretion at 1.5 × 10-3 mol/mL. But cell acylated ghrelin secretion was reduced at 1.5 × 10-3 mol/mL GO-CoA-Tat (P < 0.05). And cell acylated ghrelin synthesis was reduced at 1.5 × 10-4 and 1.5 × 10-3 mol/mL GO-CoA-Tat (P < 0.05). In accordance with acylated ghrelin level, H+-K+-ATPase activity were decreased with 1.5 × 10-4 and 1.5 × 10-3 mol/mL GO-CoA-Tat (P < 0.05). These results indicated that GOAT inhibitor decreases the acylated ghrelin level and H+-K+-ATPase activity in vitro.

MicroRNA expression profile and functional analysis reveal their roles in contact inhibition and its disruption switch of rat vascular smooth muscle cells.

Contact inhibition and its disruption of vascular smooth muscle cells (VSMCs) are important cellular events in vascular diseases. But the underlying molecular mechanisms are unclear. In this study we investigated the roles of microRNAs (miRNAs) in the contact inhibition and its disruption of VSMCs and the molecular mechanisms involved. Rat VSMCs were seeded at 30% or 90% confluence. MiRNA expression profiles in contact-inhibited confluent VSMCs (90% confluence) and non-contact-inhibited low-density VSMCs (30% confluence) were determined. We found that multiple miRNAs were differentially expressed between the two groups. Among them, miR-145 was significantly increased in contact-inhibited VSMCs. Serum could disrupt the contact inhibition as shown by the elicited proliferation of confluent VSMCs. The contact inhibition disruption accompanied with a down-regulation of miR-145. Serum-induced contact inhibition disruption of VSMCs was blocked by overexpression of miR-145. Moreover, downregulation of miR-145 was sufficient to disrupt the contact inhibition of VSMCs. The downregulation of miR-145 in serum-induced contact inhibition disruption was related to the activation PI3-kinase/Akt pathway, which was blocked by the PI3-kinase inhibitor LY294002. KLF5, a target gene of miR-145, was identified to be involved in miR-145-mediated effect on VSMC contact inhibition disruption, as it could be inhibited by knockdown of KLF5. In summary, our results show that multiple miRNAs are differentially expressed in contact-inhibited VSMCs and in non-contact-inhibited VSMCs. Among them, miR-145 is a critical gene in contact inhibition and its disruption of VSMCs. PI3-kinase/Akt/miR-145/KLF5 is a critical signaling pathway in serum-induced contact inhibition disruption. Targeting of miRNAs related to the contact inhibition of VSMCs may represent a novel therapeutic approach for vascular diseases.

Characterization and immunological activity of polysaccharides from Ixeris polycephala.

A water-soluble polysaccharide, named KMCP, was isolated and purified from edible plant Ixeris polycephala by using DEAE-52 cellulose chromatography. Its structure was determined by chemical analysis, methylation analysis, and NMR analysis, coupled with characterization by scanning electron spectroscopy (SEM). The resulting data indicated that KMCP was an arabinogalactan, with an average molecular weight of 1.95×106Da, which was mainly composed of arabinose and galactose in a relative molar ratio of 28.1% and 70.3%, respectively. The structure of KMPC was characterized as 72.5% of (1→4)-ß-Galp residues interspersed with 27.5% of (1→4,6)-ß-Galp residues in the main chain, and the branches were composed of (1→5)-α-Araf moieties or α-Araf (1→5) α-Araf (1→disaccharide moieties attached at O-6 of the (1→4,6)-ß-Galp residues. KMCP was revealed to be capable of exhibiting macrophage-mediated innate immune responses via enhancing phagocytosis of macrophages and increasing production of NO, activating NF-κB signaling pathway and promoting the mice spleen cells proliferation in a dose-dependent manner within the test concentrations (10.0-200.0µg/mL). These results suggested that KMCP could potentially be an effective and safe immunomodulator valuable to be utilized in pharmacological fields or in the development of functional foods.

Two New Thymol Derivatives from the Roots of Ageratina adenophora.

Two new thymol derivatives, 7,9-diisobutyryloxy-8-ethoxythymol (1) and 7-acetoxy-8-methoxy-9-isobutyryloxythymol (2), were isolated from fresh roots of Ageratina adenophora, together with four known compounds, 7,9-di-isobutyryloxy-8-methoxythymol (3), 9-oxoageraphorone (4), (-)-isochaminic acid (5) and (1α,6α)-10-hydroxycar-3-ene-2-one (6). Their structures were established on the basis of detailed spectroscopic analysis, and they were all isolated from the roots of A. adenophora for the first time. All the compounds were tested for their in vitro antibacterial activity toward three Gram-positive and two Gram-negative bacterial strains. Thymol derivatives 1-3 only selectively showed slight in vitro bacteriostatic activity toward three Gram-positive bacteria. The two known carene-type monoterpenes 5 and 6 were found to show moderate in vitro antibacterial activity against all five tested bacterial strains, with MIC values from 15.6 to 62.5 µg/mL. In addition, compounds 5 and 6 were further revealed to show in vitro cytotoxicity against human tumor A549, HeLa and HepG2 cell lines, with IC50 values ranging from 18.36 to 41.87 µM. However, their cytotoxic activities were inferior to those of reference compound adriamycin.

Two New Pentacyclic Triterpene Saponins from the Leaves of Akebia trifoliata.

Two new pentacyclic triterpene saponins, named akebiaoside K (1) and akebiaoside N (2), were isolated from the leaves of Akebia trifoliata, together with five known triterpenoids 3-7. They were all isolated from the leaves of A. trifoliata for the first time. Their structures were established by spectral and chemical means. Triterpenes 5 and 7 were found to show moderate in vitro cytotoxicity against human tumor A549, HeLa and HepG2 cell lines, with IC50 values ranging from 0.023 to 0.038 mM. Triterpenes 5-7 were further revealed to show significant in vitro α-glucosidase inhibitory activity with IC50 values from 0.040 to 0.220 mM, making them more potent than the reference compound acarbose (IC50 0.409 mM). Meanwhile, no obvious inhibitory effects were observed for the isolated triterpene saponins 1-4 in both bioactivity assays.

RNAi-mediated Ghrelin affects gastric H(+)-K(+)-ATPase activity and expression of GOAT-Ghrelin system in vitro.

Ghrelin has been implicated in the regulation of gastric functional development, and its physiological functions are mediated by Ghrelin-O-acyltransferase (GOAT) which is capable of generating the active form of this polypeptide hormone. However, whether and how ghrelin gene silencing may modify gastric acid secretion and GOAT-Ghrelin system is yet to be explored. The study was performed in gastric mucosal cells from weanling piglets in vitro. We evaluated the effect of ghrelin on gastric acid secretion, gene expression of GOAT and ghrelin as well as ghrelin levels by RNA interference assay. shGhrelin triggered the down-regulation of ghrelin mRNA expression (P<0.05) via an RNAi mechanism, as observed by real-time RT-PCR. In addition, shGhrelin showed reduced total ghrelin production and secretion (P<0.05) using ELISA in vitro. We also detected that GOAT mRNA expression was reduced in shGhrelin group (P<0.05), compared with control groups. In accordance with the GOAT expression, acylated ghrelin production and secretion were reduced in gastric mucosal cells and culture medium (P<0.05). Silencing of ghrelin gene achieved by RNAi-mediation inhibited the activity of H(+)-K(+)-ATPase and pepsin (P<0.05) in gastric mucosal cells. These results indicated that RNAi of Ghrelin gene inhibited the gastric acid secretion with decreased GOAT mRNA and acylated Ghrelin in gastric mucosal cells.

Early predictive efficacy of core antigen on antiviral outcomes in genotype 1 hepatitis C virus infected patients

Response-guided therapy is of limited use in developing countries because hepatitis C virus RNA detection by sensitive molecular methods is time- and labor-consuming and expen- sive. We evaluated early predictive efficacy of serum hepatitis C virus core antigen kinetics on sustained virologic response in patients with genotype 1 hepatitis C virus during pegylated interferon plus ribavirin treatment. For 478 patients recruited, hepatitis C virus RNAs were detected at baseline, and at weeks 4, 12, 24, 48, and 72 using Cobas TaqMan. Architect hepatitis C virus core antigen was performed at baseline, and weeks 4 and 12. Predictive values of hepatitis C virus core antigen on sustained virologic response were compared to hepatitis C virus RNA. In the first 12 weeks after treatment initiation the dynamic patterns of serum hepatitis C virus core antigen and hepatitis C virus RNA levels were similar in sustained virologic response, relapse, and null response patients groups. Although areas under the receiver operating characteristics curves of hepatitis C virus core antigen were lower than those of hepatitis C virus RNA at the same time points, modeling analysis showed that undetectable hepatitis C virus core antigen (rapid virological response based on hepatitis C virus core antigen) had similar positive predictive value on sustained virologic response to hepatitis C virus RNA at week 4 (90.4% vs 93.3%), and hepatitis C virus core antigen decrease greater than 1 log10 IU/mL (early virological response based on hepatitis C virus core antigen) had similar negative predictive value to hepatitis C virus RNA at week 12 (94.1% vs 95.Z%). Analysis on the validation group demonstrated a positive predictivevalue of 97.5% in rapid virological response based on hepatitis C virus core antigen and a negative predictive value of 100% in early virological response based on hepatitis C virus core antigen. In conclusion, hepatitis C virus core antigen is comparable to hepatitis C virus RNA in predicting sustained virologic response of chronic genotype 1 hepatitis C virus infected patients, and can be used to guide anti-hepatitis C virus treatment, especially in resource-limited areas.

Early predictive efficacy of core antigen on antiviral outcomes in genotype 1 hepatitis C virus infected patients.

Response-guided therapy is of limited use in developing countries because hepatitis C virus RNA detection by sensitive molecular methods is time- and labor-consuming and expensive. We evaluated early predictive efficacy of serum hepatitis C virus core antigen kinetics on sustained virologic response in patients with genotype 1 hepatitis C virus during pegylated interferon plus ribavirin treatment. For 478 patients recruited, hepatitis C virus RNAs were detected at baseline, and at weeks 4, 12, 24, 48, and 72 using Cobas TaqMan. Architect hepatitis C virus core antigen was performed at baseline, and weeks 4 and 12. Predictive values of hepatitis C virus core antigen on sustained virologic response were compared to hepatitis C virus RNA. In the first 12 weeks after treatment initiation the dynamic patterns of serum hepatitis C virus core antigen and hepatitis C virus RNA levels were similar in sustained virologic response, relapse, and null response patients groups. Although areas under the receiver operating characteristics curves of hepatitis C virus core antigen were lower than those of hepatitis C virus RNA at the same time points, modeling analysis showed that undetectable hepatitis C virus core antigen (rapid virological response based on hepatitis C virus core antigen) had similar positive predictive value on sustained virologic response to hepatitis C virus RNA at week 4 (90.4% vs 93.3%), and hepatitis C virus core antigen decrease greater than 1log10IU/mL (early virological response based on hepatitis C virus core antigen) had similar negative predictive value to hepatitis C virus RNA at week 12 (94.1% vs 95.2%). Analysis on the validation group demonstrated a positive predictive value of 97.5% in rapid virological response based on hepatitis C virus core antigen and a negative predictive value of 100% in early virological response based on hepatitis C virus core antigen. In conclusion, hepatitis C virus core antigen is comparable to hepatitis C virus RNA in predicting sustained virologic response of chronic genotype 1 hepatitis C virus infected patients, and can be used to guide anti-hepatitis C virus treatment, especially in resource-limited areas.

[The regulation of Akt signaling on axonal density after hypoxic-ischemic brain injury in neonatal rat].

OBJECTIVE: To investigate the activity of protein kinase B (Akt) and its downstream protein, glycogen synthase kinase-3beta (GSK-3beta) under hypoxia-ischemia (HI), and the possible regulation for axonal density. METHODS: Postnatal day 10 SD rats were suffered the right common carotid artery ligation and 8% mixture of oxygen and nitrogen hypoxia 2.5 h to produce HI model. The expression of total and phosphorylated Akt and GSK-3beta was detected by western blot after HI. After pretreatment of Akt inhibitor, wortmannin or LY294002, Western blot detect the expression of total and phosphorylated of Akt, GSK-3beta at 4 h and 24 h after HI. After pretreatment of wortmannin, axonal density was determined by Bielschowsky silver impregnation, and histological injury was evaluated by hematoxylin and eosin (HE) staining. RESULTS: The expression of total Akt and GSK-3beta remained unchanged after HI. p-Akt protein significantly decreased at 0.5 h, increased at 2 h and reached the highest at 4 h, returned to baseline at 8 h, declined at 24 and 48 h after HI, and finally returned to baseline again at 72 h compared with that of sham controls, p-GSK-3beta protein decreased at 0. 5 h, increased at 2 h, reached the highest at 4 h, returned to baseline at 8 and decreased at 24 h, reached the lowest at 48 h, and returned to baseline at 72 h. Wortmannin or LY294002 intervention didn't change the expression of total Akt and GSK-3beta, while decrease the p-Akt and p-GSK-3beta expression. HI cause decreased axonal density, and the histological injury of brain. Wortmannin pretreatment could aggravate the histological injury and decrease axonal density after HI. CONCLUSION: The Akt pathway is involved in axonal density and histological brain injury after HI in neonatal rat.

[(1)H-MRS study of auditory cortex in patients with presbycusis].

OBJECTIVE: To study the metabolic changes of auditory cortex in patients with presbycusis by using proton magnetic resonance spectroscopy ((1)H-MRS). METHODS: Ten normal hearing volunteers (youth group), 10 normal hearing of elderly (aged group) and 8 patients with presbycusis (presbycusis group) were checked with proton magnetic resonance spectroscopy. N-acetylaspartic acid (NAA), creatine (Cr), choline (Cho), γ-aminobutyric acid (GABA), glutamic acid (Glu) compound were measured. The differences between the groups were semi-quantitatively analyzed. RESULTS: When compared with youth group, reduced NAA/Cr, increased Cho/Cr were found in the aged group and presbycusis group (P < 0.05). GABA/Cr ratio and Glu/Cr ratio were significant difference between presbycusis group and youth group (P < 0.05). There were no significant difference in the GABA/Cr and Glu/Cr ratios in the bilateral auditory cortex between the youth group and the aged group (P > 0.05). When compared with aged group, the metabolic changes of auditory cortex in patients with presbycusis were remarkable (P < 0.05). CONCLUSIONS: (1)H-MRS is a noninvasive technique that can provide useful information concerning the metabolic changes of auditory cortex in human. In comparison to the aged group and the youth group, the changes of NAA, GABA, Cho and Glu is found in auditory cortex in patients with presbycusis.