BACKGROUND/AIMS: Programmed death-1 (PD-1) expression was investigated in CD4+ and CD8+ T cells from hepatitis B virus (HBV)-infected patients at the chronic hepatitis B (CHB) infection, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) stages. METHODS: PD-1 expression in circulating CD4+ and CD8+ T cells was detected by flow cytometry. The correlations between PD-1 expression and HBV viral load, alanine aminotransaminase (ALT) levels and aspartate aminotransferase (AST) levels were analyzed using GraphPad Prism 5.0. RESULTS: PD-1 expression in CD4+ and CD8+ T cells was significantly increased in both the CHB group and advanced-stage group (LC plus HCC). In the CHB group, PD-1 expression in both CD4+ and CD8+ T cells was positively correlated with the HBV viral load, ALT, and AST levels. However, in the LC plus HCC group, significant correlations between PD-1 expression and the clinical parameters were nearly absent. CONCLUSIONS: PD-1 expression in peripheral CD4+ and CD8+ T cells is dynamic, changes with HBV infection progression, and is related to HBV viral load and liver function, especially in CHB. PD-1 expression could be utilized as a potential clinical indicator to determine the extent of virus replication and liver injury.
Adult ; CD4-Positive T-Lymphocytes/*metabolism ; CD8-Positive T-Lymphocytes/*metabolism ; Carcinoma, Hepatocellular ; Disease Progression ; Female ; Hepatitis B, Chronic/*diagnosis/immunology ; Humans ; Liver Cirrhosis ; Liver Neoplasms ; Male ; Programmed Cell Death 1 Receptor/*metabolism ; Viral Load

OBJECTIVE: Vascular endothelial growth factor (VEGF) interaction with its receptor, VEGFR-3/Flt-4, regulates lymphangiogenesis. VEGFR-3/Flt-4 expression in cancer cells has been correlated with clinical stage, lymph node metastasis, and lymphatic invasion. The objective of this study is to identify a VEGFR-3/Flt-4-interacting peptide that could be used to inhibit VEGFR-3 for ovarian cancer therapy. METHODS: The extracellular fragment of recombinant human VEGFR-3/Flt-4 (rhVEGFR-3/Flt-4) fused with coat protein pIII was screened against a phage-displayed random peptide library. Using affinity enrichment and enzyme-linked immunosorbent assay (ELISA) screening, positive clones of phages were amplified. Three phage clones were selected after four rounds of biopanning, and the specific binding of the peptides to rhVEGFR-3 was detected by ELISA and compared with that of VEGF-D. Immunohistochemistry and immunofluorescence analyses of ovarian cancer tissue sections was undertaken to demonstrate the specificity of the peptides. RESULTS: After four rounds of biopanning, ELISA confirmed the specificity of the enriched bound phage clones for rhVEGFR-3. Sequencing and translation identified three different peptides. Non-competitive ELISA revealed that peptides I, II, and III had binding affinities for VEGFR-3 with Kaff (affinity constant) of 16.4+/-8.6 microg/mL (n=3), 9.2+/-2.1 microg/mL (n=3), and 174.8+/-31.1 microg/mL (n=3), respectively. In ovarian carcinoma tissue sections, peptide III (WHWLPNLRHYAS), which had the greatest binding affinity, also co-localized with VEGFR-3 in endothelial cells lining lymphatic vessels; its labeling of ovarian tumors in vivo was also confirmed. CONCLUSION: These finding showed that peptide III has high specificity and activity and, therefore, may represent a potential therapeutic approach to target VEGF-VEGFR-3 signaling for the treatment or diagnosis of ovarian cancer.
Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Ovarian Neoplasms/*therapy ; *Peptide Library ; Sequence Analysis, DNA ; Signal Transduction/physiology ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor Receptor-3/antagonists & inhibitors/*metabolism

As part of our ongoing influenza surveillance program in South China, 19 field strains of H9N2 subtype avian influenza viruses (AIVs) were isolated from dead or diseased chicken flocks in Guangdong province, South China, between 2012 and 2013. Hemagglutinin (HA) genes of these strains were sequenced and analyzed and phylogenic analysis showed that 12 of the 19 isolates belonged to the lineage h9.4.2.5, while the other seven belonged to h9.4.2.6. Specifically, we found that all of the viruses isolated in 2013 belonged to lineage h9.4.2.5. The lineage h9.4.2.5 viruses contained a PSRSSRdownward arrowGLF motif at HA cleavage site, while the lineage h9.4.2.6 viruses contained a PARSSRdownward arrowGLF at the same position. Most of the isolates in lineage h9.4.2.5 lost one potential glycosylation site at residues 200-202, and had an additional one at residues 295-297 in HA1. Notably, 19 isolates had an amino acid exchange (Q226L) in the receptor binding site, which indicated that the viruses had potential affinity of binding to human like receptor. The present study shows the importance of continuing surveillance of new H9N2 strains to better prepare for the next epidemic or pandemic outbreak of H9N2 AIV infections in chicken flocks.
Animals ; *Chickens ; China ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry/*genetics/metabolism ; Influenza A Virus, H9N2 Subtype/*genetics/metabolism ; Influenza in Birds/virology ; Phylogeny ; Poultry Diseases/*virology ; Sequence Analysis, RNA/veterinary

PURPOSE: To investigate the distribution of CD44+/CD24- cells in breast cancers in relation to tumor size before and after the administration of neoadjuvant chemotherapy. METHODS: CD44+/CD24- tumor cells obtained from breast cancer specimens were characterized in vivo and in vitro using tumor formation assays and mammosphere generation assays, respectively. The distribution of CD44+/CD24- tumor cells in 78 breast cancer specimens following administration of neoadjuvant chemotherapy was also evaluated using immunofluorescence assays, and this distribution was compared with the extent of tumor invasion predicted by Response Evaluation Criteria in Solid Tumours (RECIST). RESULTS: In 27/78 cases, complete remission (CR) was identified using RECIST. However, 18 of these CR cases were associated with a scattered distribution of tumor stem cells in the outline of the original tumor prior to neoadjuvant chemotherapy. After neoadjuvant chemotherapy, 24 cases involved cancer cells that were confined to the tumor outline, and 21 cases had tumor cells or tumor stem cells overlapping the tumor outline. In addition, there were 6 patients who were insensitive to chemotherapy, and in these cases, both cancer cells and stem cells were detected outside the contours of the tumor volume imaged prior to chemotherapy. CONCLUSION: CD44+/CD24- tumor cells may be an additional parameter to evaluate when determining the extent of breast cancer invasion.
Breast ; Breast Neoplasms ; Fluorescent Antibody Technique ; Humans ; Neoplasm Invasiveness ; Neoplastic Stem Cells ; Stem Cells ; Tumor Burden

No abstract available.
Anti-N-Methyl-D-Aspartate Receptor Encephalitis* ; Humans ; Lupus Erythematosus, Systemic*

PURPOSE: To evaluate social adjustment and related factors among Chinese children with Down syndrome (DS). PATIENTS AND METHODS: A structured interview and Peabody Picture Vocabulary Test (PPVT) were conducted with a group of 36 DS children with a mean age of 106.28 months, a group of 30 normally-developing children matched for mental age (MA) and a group of 40 normally-developing children matched for chronological age (CA). Mean scores of social adjustment were compared between the three groups, and partial correlations and stepwise multiple regression models were used to further explore related factors. RESULTS: There was no difference between the DS group and the MA group in terms of communication skills. However, the DS group scored much better than the MA group in self-dependence, locomotion, work skills, socialization and self-management. Children in the CA group achieved significantly higher scores in all aspects of social adjustment than the DS children. Partial correlations indicate a relationship between social adjustment and the PPVT raw score and also between social adjustment and age (significant r ranging between 0.24 and 0.92). A stepwise linear regression analysis showed that family structure was the main predictor of social adjustment. Newborn history was also a predictor of work skills, communication, socialization and self-management. Parental education was found to account for 8% of self-dependence. Maternal education explained 6% of the variation in locomotion. CONCLUSION: Although limited by the small sample size, these results indicate that Chinese DS children have better social adjustment skills when compared to their mental-age-matched normally-developing peers, but that the Chinese DS children showed aspects of adaptive development that differed from Western DS children. Analyses of factors related to social adjustment suggest that effective early intervention may improve social adaptability.
Adolescent ; Asian Continental Ancestry Group/*psychology ; Child ; Child, Preschool ; China ; Communication ; Down Syndrome/ethnology/*psychology ; Female ; Humans ; Male ; *Social Adjustment ; Socioeconomic Factors

PURPOSE: It is widely accepted that aldehyde dehydrogenase (ALDH) activity is a signature of breast cancer stem cells, and high activity has been reported to be associated with poor clinical outcome. The aim of this study was to assess the expression of members of the ALDH family of isozymes in breast cancer tissues and to evaluate the implications of the results. METHODS: We analyzed paraffin-embedded tumor tissue from 160 patients with breast cancer. Immunohistochemistry (IHC) staining was performed on the slides using antibodies against different ALDH family members. We collated the IHC results with patient clinical characteristics and determined their prognostic value. In addition, we analyzed normal, hyperplastic, and carcinomatous tissues in situ to check their ALDH distributions. RESULTS: All the tested ALDH members were detected in the various tissue types, but at different levels. Only ALDH 1A3 was found to be significantly associated with distant metastasis (p=0.001), disease-free survival (p<0.001), and overall survival (p<0.001). CONCLUSION: The level of ALDH 1A3 in breast cancer tissue is a predictive marker of a poor clinical outcome.
Aldehyde Dehydrogenase* ; Antibodies ; Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Humans ; Immunohistochemistry ; Isoenzymes ; Neoplasm Metastasis ; Neoplastic Stem Cells ; Prognosis ; Stem Cells

PURPOSE: The purpose of this study was to assess the value of ovarian ablation using goserelin in premenopausal patients with stage II/III hormone receptor-positive breast cancer without chemotherapy-induced amenorrhea (CIA). MATERIALS AND METHODS: We retrospectively reviewed the data of breast patients treated between October 1999 and November 2007 without CIA. The Kaplan-Meier method was used for calculation of the survival rate. Log rank method and Cox regression analysis were used for univariate and multivariate prognostic analysis. RESULTS: The median follow-up period was 61 months. Initially, 353 patients remained without CIA after chemotherapy and 98 among those who received goserelin and tamoxifen (TAM). In univariate analysis, goserelin improved locoregional recurrence-free survival (LRFS) (98.9% vs. 94.1%, p=0.041), distant metastasis-free survival (DMFS) (85.4% vs. 71.9%, p=0.006), disease-free survival (DFS) (85.4% vs. 71.6%, p=0.005), and overall survival (OS) (93.5% vs. 83.5%, p=0.010). In multivariate analysis, goserelin treatment was an independent factor influencing DMFS (hazard ratio [HR], 1.603; 95% confidence interval [CI], 1.228 to 2.092; p=0.001), DFS (HR, 1.606; 95% CI, 1.231 to 2.096; p=0.001), and OS (HR, 3.311; 95% CI, 1.416 to 7.742; p=0.006). In addition, treatment with goserelin resulted in significantly improved LRFS (p=0.039), DMFS (p=0.043), DFS (p=0.036), and OS (p=0.010) in patients aged < 40 years. In patients aged > or = 40 years, goserelin only improved DMFS (p=0.028) and DFS (p=0.027). CONCLUSION: Ovarian ablation with goserelin plus TAM resulted in significantly improved therapeutic efficacy in premenopausal patients with stage II/III hormone receptor-positive breast cancer without CIA.
Amenorrhea* ; Breast ; Breast Neoplasms* ; Disease-Free Survival ; Drug Therapy ; Female ; Follow-Up Studies ; Goserelin* ; Humans ; Multivariate Analysis ; Premenopause ; Retrospective Studies ; Survival Rate ; Tamoxifen

PURPOSE: This study was conducted to investigate the prognostic value of lymph node ratio (LNR) in stage II/III breast cancer patients who undergo mastectomy after neoadjuvant chemotherapy. MATERIALS AND METHODS: Clinical and pathological data describing stage II/III breast cancer patients were included in this retrospective study. The primary outcomes were locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). RESULTS: Among 277 patients, there were 43 ypN0, 64 ypN1, 89 ypN2, and 81 ypN3 cases. Additionally, there were 43, 57, 92 and 85 cases in the LNR 0, 0.01-0.20, 0.21-0.65, and > 0.65 groups, respectively. The median follow-up was 49.5 months. Univariate analysis showed that both ypN stage and LNR were prognostic factors of LRFS, DMFS, DFS, and OS (p < 0.05). Multivariate analysis showed that LNR was an independent prognostic factor of LRFS, DMFS, DFS, and OS (p < 0.05), while ypN stage had no effect on prognosis (p > 0.05). CONCLUSION: The integrated use of LNR and ypN may be suitable for evaluation the prognosis of stage II/III breast cancer patients who undergo mastectomy after neoadjuvant chemotherapy.
Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Drug Therapy* ; Follow-Up Studies ; Humans ; Lymph Nodes* ; Mastectomy* ; Multivariate Analysis ; Neoadjuvant Therapy ; Prognosis* ; Retrospective Studies

The prevalence and genotype of Toxoplasma gondii infection in dogs in Henan Province, Central China was investigated. A total of 125 blood samples were collected from pet dogs during April to June 2013, and all samples were examined by indirect hemagglutination antibody test (IHA) and nested PCR. The overall T. gondii prevalence in pet dogs was 24.0% (30/125), with 20.8% (26/125) in IHA and 10.4% (13/125) in PCR, respectively. No statistical associations were found between animal gender and age and the prevalence of T. gondii infection. Thirteen positive DNA samples were genotyped using 11 PCR-RFLP markers, including SAG1, (3'+5') SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico. Of these, only 2 samples were genotyped with complete data for all loci, and a novel genotype (type III at SAG3 and GRA6 loci, and type I at other loci) was identified. This is the first report of genetic characterization of T. gondii infection in dogs in China.
Animals ; China/epidemiology ; Dog Diseases/*epidemiology/*parasitology ; Dogs ; Genotype ; Hemagglutination Tests ; Pets ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Prevalence ; Toxoplasma/*classification/genetics/*isolation & purification ; Toxoplasmosis, Animal/*epidemiology/*parasitology