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1.
Autoimmunity ; : 1-7, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790283

RESUMO

High mobility group box 1 (HMGB1) played pathogenic role in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Recent findings demonstrated that Toll-like receptor 9 (TLR9) was involved in B cell tolerance breaking of autoimmune disease, including AAV. Here, we investigated the effect of HMGB1 on TLR9 in B cells of AAV. In the present work, patients with myeloperoxidase (MPO)-AAV in active stage were recruited. Intracellular TLR9 expression in various B cell subpopulations of the whole blood was detected by flow cytometry and the correlation with clinical data was analysed. Our results showed that intracellular TLR9 expression in B cells, memory B cells and plasmablasts correlated with erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). In particular, TLR9 expression in plasma cells correlated with ESR, CRP, serum creatinine, eGFR, and Birmingham Vasculitis Activity Score. To further explore the effect of HMGB1 on B cell, peripheral blood mononuclear cells (PBMCs) from AAV patients were isolated. After stimulated with HMGB1, TLR9 expression in various B cell subpopulations and proliferation ratio of live B cells were analysed by flow cytometry. We found that TLR9 expression in plasma cells and the proliferation ratio of live B cells by HMGB1 stimulation were significantly upregulated compared with the control group. Therefore, TLR9 expression in plasma cells was associated with disease activity of MPO-AAV. HMGB1 could enhance TLR9 expression in plasma cells and B cell proliferation. These indicated a role of HMGB1 on TLR9 in B cells in MPO-AAV, which would provide potential clues for intervention strategies.

2.
BMJ Open Diabetes Res Care ; 7(1): e000817, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798904

RESUMO

Objective: Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal disease. Emerging evidence suggests that complement activation is involved in the pathogenesis of DN. The aim of this study was to investigate the pathogenic role of C3a and C3a receptor (C3aR) in DN. Research design and methods: The expression of C3aR was examined in the renal specimen of patients with DN. Using a C3aR gene knockout mice (C3aR -/-), we evaluated kidney injury in diabetic mice. The mouse gene expression microarray was performed to further explore the pathogenic role of C3aR. Then the underlying mechanism was investigated in vitro with macrophage treated with C3a. Results: Compared with normal controls, the renal expression of C3aR was significantly increased in patients with DN. C3aR -/- diabetic mice developed less severe diabetic renal damage compared with wild-type (WT) diabetic mice, exhibiting significantly lower level of albuminuria and milder renal pathological injury. Microarray profiling uncovered significantly suppressed inflammatory responses and T-cell adaptive immunity in C3aR -/- diabetic mice compared with WT diabetic mice, and this result was further verified by immunohistochemical staining of renal CD4+, CD8+ T cells and macrophage infiltration. In vitro study demonstrated C3a can enhance macrophage-secreted cytokines which could induce inflammatory responses and differentiation of T-cell lineage. Conclusions: C3aR deficiency could attenuate diabetic renal damage through suppressing inflammatory responses and T-cell adaptive immunity, possibly by influencing macrophage-secreted cytokines. Thus, C3aR may be a promising therapeutic target for DN.

3.
Childs Nerv Syst ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31786633

RESUMO

PURPOSE: The acquired Chiari type I malformation is a rare late complication of supratentorial shunting in children which is often accompanied by abnormal cranial vault thickening. Several surgical treatments for this disease have been proposed including supratentorial skull enlarging procedures and subtentorial craniotomy. But there is still debate about the best treatment strategy for this disease. METHOD AND RESULTS: We reviewed the current knowledge of this disease in the paper. We illustrated one patient of symptomatic acquired Chiari type I malformation who had cysto-peritoneal (C-P) shunting and ventriculoperitoneal (V-P) shunting. We observed the CSF flow dynamic of this patient at different periods. The acquired Chiari type I malformation disappeared on imaging after thinning the occipital planum combined with the standard surgical therapy of Chiari decompression. The symptoms of the patient were relieved after surgery. CONCLUSION: Overshunting manifestations require prompt recognition and management. Preventive measures should be taken which include making a stringent selection of cases being considered for surgery, avoiding C-P drainage, and placing of a programmable valve as initial treatment of intracranial arachnoid cysts (AC) if shunting is considered.

4.
Mol Genet Genomic Med ; : e1063, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31793236

RESUMO

BACKGROUND: Methylmalonic acidemia (MMA) is an autosomal recessive genetic disorder involving the metabolism of organic acids. METHODS: Here, we report the case of a patient who developed acute metabolic crisis after vaccination and was diagnosed with cblA type MMA after hospitalization. RESULTS: Further examination revealed a homozygous pathogenic variant in the MMAA gene that caused the disease in the patient but did not conform to Mendelian inheritance. Using chromosomal microarray analysis, maternal uniparental disomy (UPD) was found on chromosome 4q26-q35.2 of the patient. The MMAA gene of the patient was inherited only from the mother and carried the same pathogenic variant on both alleles of chromosome 4. MMAA gene expression levels in whole blood were detected by real-time PCR. CONCLUSION: The nonsense pathogenic variant, NM_172250.2:c.742C>T (p.Gln248*), carried by the patient leads to a premature termination of transcription of the gene, thereby resulting in partial loss of protein function while retaining some others. Segmental UPD 4 is rare, and to our knowledge, has not been reported previously.

5.
Bioinformatics ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31755899

RESUMO

MOTIVATION: Although genome-wide association studies (GWAS) have deepened our understanding of the genetic architecture of complex traits, the mechanistic links that underlie how genetic variants cause complex traits remains elusive. To advance our understanding of the underlying mechanistic links, various consortia have collected a vast volume of genomic data that enable us to investigate the role that genetic variants play in gene expression regulation. Recently, a collaborative mixed model (CoMM) (Yang et al., 2018a) was proposed to jointly interrogate genome on complex traits by integrating both theGWAS dataset and the expression quantitative trait loci (eQTL) dataset. Although CoMM is a powerful approach that leverages regulatory information while accounting for the uncertainty in using an eQTL dataset, it requires individual-level GWAS data and cannot fully make use of widely available GWAS summary statistics. Therefore, statistically efficient methods that leverages transcriptome information using only summary statistics information from GWAS data are required. RESULTS: In this study, we propose a novel probabilistic model, CoMM-S2, to examine the mechanistic role that genetic variants play, by using only GWAS summary statistics instead of individual-level GWAS data. Similar to CoMM which uses individual-level GWAS data, CoMM-S2 combines two models: the first model examines the relationship between gene expression and genotype, while the second model examines the relationship between the phenotype and the predicted gene expression from the first model. Distinct from CoMM, CoMM-S2 requires only GWAS summary statistics. Using both simulation studies and real data analysis, we demonstrate that even though CoMM-S2 utilizes GWAS summary statistics, it has comparable performance as CoMM, which uses individual-level GWAS data. AVAILABILITY AND IMPLEMENTATION: The implement of CoMM-S2 is included in the CoMM package that can be downloaded from https://github.com/gordonliu810822/CoMM. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

6.
Prenat Diagn ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31671222

RESUMO

OBJECTIVE: To analyze the fetal fraction, fetal sex, and chromosomal aneuploidy in multiple pregnancies using noninvasive prenatal testing (NIPT). METHOD: A total of 362 pregnant women including 203 singleton pregnancies, 69 twins, and 90 higher-order multiple pregnancies were recruited. Fetal fractions estimated by size ratio-based and Y chromosome-based approaches in singleton pregnancies with male fetus were used as source data to establish the model. The model was then applied to multiple pregnancies for fetal fraction estimation. By comparing the fetal fractions estimated by size ratio to those estimated by Y chromosome or autosomal chromosomes, fetal sex and chromosomal aneuploidy can be analyzed. RESULTS: The size ratio-based approach has been well established in estimating fetal fractions for twin and higher-order multiple pregnancies. Fetal fraction had a positive correlation with gestational age in twin and triplet pregnancies. Fetal sex was determined with accuracies of 98.6% (95% CI, 92.19%-99.96%) in twins and 97.6% (95% CI, 91.76%-99.71%) in triplet pregnancies. Four trisomy 21, one trisomy 18, and one trisomy 13 cases were detected by NIPT. Two trisomy 21 singleton pregnancies and one trisomy 21 twin pregnancy were confirmed by karyotyping. CONCLUSION: Fetal sex and chromosomal aneuploidy in multiple pregnancies can be determined using NIPT.

7.
Mol Med Rep ; 20(5): 4665-4673, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702032

RESUMO

Bone marrow­derived mesenchymal stem cells (BMSCs) possess potential therapeutic properties for treating patients with chronic obstructive pulmonary disease (COPD), which is characterized by emphysema and obstructive sleep apnea (OSA). However, their effects on overlap syndrome (OS) remain unclear. We investigated the potential therapeutic effects and possible mechanisms of BMSC transplantation in OS rats. To generate the OS model in rats, the animals underwent daily exposure to cigarette smoke and intermittent hypoxia. BMSCs were intravenously injected into rats. At 4 weeks post­transplantation, the severity of emphysema was assessed by lung hematoxylin and eosin (H&E) staining. The levels of oxidative stress and the malondialdehyde (MDA) and superoxide dismutase (SOD) contents in serum and lung were detected. The apoptosis of alveolar septal cells was also detected by TUNEL assay. Finally, we determined the expression of CD31 and VWF in lung tissues by an immunohistochemical (IHC) assay. It was found that BMSCs were able to migrate to the injured lung and aorta tissues. In lung tissues, transplanted BMSCs, some of which had differentiated into endotheliocytes, were found in the alveolar walls. The mean linear intercept (MLI) and pathological scores were higher and the mean alveolar number (MAN) was lower in the OS group than these parameters in the control group. These values were significantly reduced in the OS+BMSC group compared to those in the OS group. The MDA content was decreased and SOD activity was increased in the OS+BMSC group compared to those in the OS group. The apoptotic index of alveolar wall cells in the OS group was higher than that in the OS+BMSC group. The expression levels of CD31 and VWF in alveolar wall cells in the OS group were lower than those in the OS+BMSC group. These results indicate that BMSCs may inhibit the progression of emphysema in the OS model by differentiating into endotheliocytes and suppressing the apoptosis of endotheliocytes and oxidative stress. There is a possibility that the release of growth factors and structural support may be a determinant for the regenerative effects observed following treatment with BMSCs.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31736177

RESUMO

Transition metal-catalyzed ethylene copolymerization with polar monomers is a highly challenging reaction. After decades of research, the scope of suitable comonomer substrates has expanded from special to fundamental polar monomers and, recently, to 1,1-disubstituted ethylenes. In this contribution, we aim to describe a direct and tandem strategy to realize ethylene copolymerization with various 1,2-disubstituted ethylenes. The direct route is sensitive to steric effects from both the comonomers and the catalyst. In the tandem route, ruthenium-catalyzed ethenolysis can convert 1,2-disubstituted ethylenes to terminal olefins that can be subsequently copolymerized with ethylene to afford polar functionalized polyolefins. The one-pot, two-step tandem route is highly versatile and efficient in dealing with challenging substrates. This work is a step forward in terms of expanding the substrate scope for transition metal-catalyzed ethylene copolymerization with polar-functionalized comonomers.

9.
Bioorg Med Chem Lett ; 29(24): 126772, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31711785

RESUMO

Inhibition of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) to prevent brain ß-amyloid (Aß) peptide's formation is a potential effective approach to treat Alzheimer's disease. In this report we described a structure-based optimization of a series of BACE1 inhibitors derived from an iminopyrimidinone scaffold W-41 (IC50 = 7.1 µM) by Wyeth, which had good selectivity and brain permeability but low activity. The results showed that occupying the S3 cavity of BACE1 enzyme could be an effective strategy to increase the biological activity, and five compounds exhibited stronger inhibitory activity and higher liposolubility than W-41, with L-5 was the most potent inhibitor against BACE1 (IC50 = 0.12 µM, logP = 2.49).

10.
World Neurosurg ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31756500

RESUMO

OBJECTIVE: Ventriculostomy-related infection (VRI) is associated with potential serious morbidity, extended hospitalization duration, increased healthcare costs, and mortality. We assessed the effectiveness of a pragmatic risk stratification pathway for external ventricular drain (EVD) management, allowing for surgical decision-making, in reducing the rate of VRIs. METHODS: Two studies were performed concurrently. A retrospective audit of EVD infection rates and outcomes in our unit across three hospitals was conducted from January to December 2014. The second prospective study compared the same variables during the implementation of the EVD pathway across the three sites from January 2015 to December 2016. RESULTS: The number of patients requiring EVDs increased from 2014 to 2016 (165 vs. 189 vs. 197 patients, respectively), with a significant increase in patients with intraventricular hemorrhage (P=.009). Despite increasing risk, overall EVD infections decreased during the implementation period, from 4.8% (8/165) in 2014 to 3.7% in 2015 (7/189) and 2.0% in 2016 (4/197, P = .33). In two sites (Site 1, 2.0% vs. 2.1% vs. 1.9%, and Site 2, 4.7% vs. 5.0% vs. 5.3%), transition to the EVD risk stratification pathway maintained already low infection rates; in Site 3, EVD infections decreased from 6.8% (5/73) to 3.9% (4/102) and 0% (0/86, P = .06). CONCLUSION: The introduction of a pragmatic evidence-based risk stratification pathway, in which different options for EVD management are incorporated, results in low EVD infection rates across a multi-site institutional practice. Our results are comparable to published protocols involving the implementation of standard care bundles and/or antibacterial EVDs alone, in reducing VRIs.

11.
Cell Rep ; 29(7): 1862-1877.e7, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31722203

RESUMO

Autophagy plays a critical role in the maintenance of immunological memory. However, the molecular mechanisms involved in autophagy-regulated effector memory formation in CD8+ T cells remain unclear. Here we show that deficiency in NIX-dependent mitophagy leads to metabolic defects in effector memory T cells. Deletion of NIX caused HIF1α accumulation and altered cellular metabolism from long-chain fatty acid to short/branched-chain fatty acid oxidation, thereby compromising ATP synthesis during effector memory formation. Preventing HIF1α accumulation restored long-chain fatty acid metabolism and effector memory formation in antigen-specific CD8+ T cells. Our study suggests that NIX-mediated mitophagy is critical for effector memory formation in T cells.

12.
Mol Med Rep ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31746399

RESUMO

Bone marrow mesenchymal stem cells (BM­MSCs) are important for postnatal angiogenesis and are suitable for use in construction of blood vessels by tissue engineering. The present study aimed to investigate the influence of recombination signal binding protein for immunoglobulin kappa J region (RBP­JK) on the differentiation of BM­MSCs into vascular endothelial cells, and to assess the underlying mechanisms. BM­MSCs were isolated and identified by flow cytometry. Lentiviral vectors encoding RBP­JK shRNA (shRBPJK) were constructed to knockdown RBP­JK expression and endothelial differentiation of BM­MSCs was induced. The experimental groups were treated with: empty lentiviral vector (vector group), growth factors (bFGF and VEGF; induced group), shRBPJK (shRBPJK group), and growth factors + shRBPJK (induced + shRBPJK group). The expression of endothelial markers, vascular endothelial growth factor receptor 2 (Flk­1), and von Willebrand factor (vWF) were detected by immunofluorescence. Additionally, in vitro blood vessel formation and phagocytosis were assessed using acetylated LDL, Dil complex and the underlying molecular mechanisms evaluated by western blotting. BM­MSCs were separated and transduced with shRBPJK to reduce RBP­JK expression. Compared with the vector group, the expression of the endothelial cell markers, Flk­1 and vWF, in vitro tubule formation, and phagocytosis ability increased, while the expression levels of p­AKT/AKT and p­NF­κB/NF­κB were significantly decreased (P<0.05) in the induced, shRBPJK, and induced + shRBPJK groups. Compared with the induced group, the expression of Flk­1 and vWF, the number of tubules, and phagocytosis were higher in the induced + shRBPJK group, while the expression levels of p­AKT/AKT and p­NF­κB/NF­κB were lower (P<0.05). Collectively, the present data indicated that silencing of RBP­JK promotes the differentiation of MSCs into vascular endothelial cells, and this process is likely regulated by AKT/NF­κB signaling.

13.
Neurosci Lett ; : 134640, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31759083

RESUMO

Dopaminergic (DAergic) degeneration and abnormal α-synuclein (α-syn) expression, phosphorylation and aggregation are observed in both the nigrostriatal system (NSS) and enteric nervous system (ENS) of patients with Parkinson's disease (PD). Whether these alterations in α-syn and DAergic neurons occur synchronously in the two nervous systems or follow a process that spreads from the gut to the brain remains a subject of debate. Here, in MPTP-intoxicated cynomolgus monkeys, we showed a parallel DAergic degeneration in the colon as well as in the substantia nigra and striatum (SN/STR), as indicated by reduced expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT). In addition, we observed a simultaneous increase in the concentrations of total, phosphorylated, and oligomeric α-syn in the colon and SN/STR. Moreover, we identified that the above changes in α-syn were associated with an increase in the expression of polo-like kinase 2 (PLK2), an enzyme that promotes α-syn phosphorylation, and a decrease in the activity of protein phosphatase 2A (PP2A), an enzyme that facilitates α-syn dephosphorylation. Because the colonic ENS can be readily analyzed using routine biopsies, the shared pathological features between the colonic ENS and the brain NSS found in this study provide useful information for assessing and understanding the neuropathology in PD patients using colonic biopsies.

14.
Mikrochim Acta ; 186(12): 835, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31758331

RESUMO

A dual (colorimetric and fluorometric) method is described for sensitive and selective determination of the herbicide glyphosate. It is based on the use of a system composed of polyethylenimine-capped NaGdF4:Yb,Er upconversion nanoparticles (UCNPs), copper(II) ions, hydrogen peroxide and 3,3',5,5'-tetramethylbenzidine. The physicochemical and photophysical properties of the polyethylenimine-capped UCNPs were characterized by various spectroscopic and microscopic techniques. The fluorescence of the UCNPs (with main emission peaks at 548 and 660 nm under 980 nm excitation) is reduced in the presence of Cu(II) because of the formation of a blue oxidation product of 3,3',5,5'-tetramethylbenzidine as a result of the peroxidase mimicking activity of Cu(II). In the presence of glyphosate, its strong affinity for Cu(II) leads to the formation of N-(phosphonomethyl)glycine copper(II) complexes. This inhibits the quenching ability and catalysis activity of Cu(II). Hence, fluorescence is increasingly less reduced. Fluorescence at 660 nm increases linearly in the 0.05 to 125 µg·mL-1 glyphosate concentration range and the detection limit is found 9.8 ng·mL-1. The colorimetric assay (performed at 652 nm) has a detection ranges from 5 to 125 µg·mL-1, and the limit of detection is 1 µg·mL-1. Graphical abstractSchematic representation of UCNP-H2O2-TMB-Cu(II) mixed system for optical determinations of glyphosate.

15.
Int Immunopharmacol ; 77: 105984, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31677501

RESUMO

Ampelopsin (Amp), a natural flavonoid found in the vine tea of Ampelopsis grossedentata, exhibited anti-cancer, anti-oxidant, anti-inflammatory, anti-apoptosis and hepatoprotective properties. The current study instigates the protective effect of Amp on carbon tetrachloride (CCl4)-induced hepatic fibrosis and explores its underlying mechanisms. The results indicated Amp decreased the levels of liver injury markers. Amp inhibited liver fibrosis, as indicated by decreases in hepatic collagen deposition, extracellular matrix (ECM) deposition and α-smooth muscle actin (α-SMA). Amp blocked the activation of hepaticstellate cells (HSCs) by decreasing the expression of collage I, α-SMA, tissue inhibitor of matrix metalloproteinases (TIMPs) 1, transforming growth factor (TGF)-ß1, phosphorylated Smad3 (p-Smad3) and increasing the expression of matrix metalloproteinases (MMPs) 9 and SIRT1 in the model of liver fibrosis and cultured HSCs. The sirtuin 1 (SIRT1) specific inhibitor Sirtinol activated the TGF-ß1/Smad3 pathway and enhanced ECM accumulation. Attractively, Amp up-regulates the expression of autophagy-related proteins microtubule-associated protein light chain three II (LC3-II) and Beclin-1 in vivo and in vitro. However, depletion of autophagy by specific inhibitor 3-MA obviously abolished the inhibiting effect of Amp on HSC activation and hepatic fibrosis. Conclusively, these results suggest that Amp could decrease CCl4-induced hepatic fibrosis through regulating the SIRT1/TGF-ß1/Smad3 and autophagy pathway.

16.
Int J Biol Macromol ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31726162

RESUMO

Polysaccharide from Grifola frondosa is an excellent metal-ion chelating agent owing to its distinctive structure and outstanding functional activities. Our previous research has successfully synthesized novel organic chromium derived from the chelation ofG. frondosapolysaccharide-chromium (III) [GFP-Cr(III)]. The purpose of present research was to reveal the hypoglycemic and hypolipidemic mechanism of GFP-Cr(III), and its relationship with the modulation of intestinal microflora. Successful fabrication of GFP-Cr(III) was verified by thermogravimetric analysis (TGA), powder X-ray diffraction (XRD) and 1H NMR spectrum.The hypoglycemic and hypolipidemic effects were examined using type 2 diabetic mice induced by a high-fat diet (HFD) and streptozocin (STZ). Results indicated that GFP-Cr(III) intervention improved abnormal serum biochemical indicators (triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and glucose), inhibited lipid accumulation and steatosis in the liver. Metagenomic analysis revealed that GFP-Cr(III) treatment produced obvious changes on the intestinal microflora in T2DM mice. Thecorrelationnetwork analysis further revealed that the serum and hepatic lipid profiles were positively correlated with Streptococcus and Enterococcus, but negatively correlated with Enterorhabdus, Ruminococcaceae-UCG-011, Coriobacteriaceae and Micrococcaceae. Meanwhile, oral administration with GFP-Cr(III) regulated the mRNA expression related to glucose and lipid metabolism. These results of present study suggest that GFP-Cr(III) could be used as potential functional food ingredients for the amelioration of hyperglycemia and hyperlipidemia.

18.
Vaccine ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31732325

RESUMO

In the U.S., measles, mumps, and rubella vaccination is recommended as two vaccine doses. A third dose of measles-mumps-rubella (MMR) vaccine is being administered in certain situations (e.g., identified seronegativity and during outbreaks). We studied rubella-specific humoral immunity (neutralizing antibody, enzyme-linked immunosorbent assay/ELISA IgG titer and antibody avidity) and the frequencies of antigen-specific memory B cells before and after a third dose of MMR-II in 109 female participants of childbearing age (median age, 34.5 years old) from Olmsted County, MN, with two documented prior MMR vaccine doses. The participants were selected from a cohort of 1117 individuals if they represented the high and the low ends of the rubella-specific antibody response spectrum. Of the 109 participants, we identified four individuals (3.67% of all study participants; 7.14% of the low-responder group) that were seronegative at Baseline (rubella-specific ELISA IgG titers <10 IU/mL), suggesting a lack of protection against rubella before receipt of a third MMR vaccine dose. The peak geometric mean neutralizing antibody titer one month following the third dose of MMR vaccine for the cohort was 243 NT50 (CI; 241, 245), which is expected for a cohort with two doses of MMR, and the peak geometric mean IgG titer was 150 IU/mL (CI; 148, 152) with no seronegative individuals at Day 28. One-third of all subjects (31.8% for the neutralizing antibody; 30.8% for the IgG titer) experienced a significant boost (≥4-fold) of antibody titers one month following vaccination. Antibody titers and other tested immune-response variables were significantly higher in the high-responder group compared to the low-responder group. The frequencies of rubella-specific memory B cells were modestly associated with the antibody titers. Our study suggests the importance of yet unknown inherent biologic and immune factors for the generation and maintenance of rubella-vaccine-induced humoral immune responses.

19.
J Clin Pathol ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31732618

RESUMO

AIMS: The aim of this study is to analyse differences in clinicopathologic features among reclassified human epidermal growth factor receptor-2 (HER2) fluorescence in situ hybridization (FISH) results in breast cancers according to 2018 guidelines. METHODS: According to different ratios of HER2 copy numbers to chromosome 17 centromere numbers (HER2/CEP17) and average HER2 copy numbers, 3795 invasive breast cancers were classified into six groups. Clinicopathologic features were collected and compared among different FISH groups. RESULTS: There were no statistically significant differences about HER2 positive rate between 2013 and 2018 guidelines (p=0.518). After re-evaluating these cases according to 2018 guidelines, the cases that converted to a HER2 positive status had clinicopathologic features similar to samples in group 1 (ratio ≥2.0, HER2 ≥4.0). Compared with group 5 (ratio <2.0, HER2 <4.0), the cases in groups 1 had higher histological grade, more frequent occurrence of negative oestrogen receptor and progesterone receptor status and a higher Ki67 index. The samples in group 4 (ratio <2.0, 4.0≤HER 2<6.0) showed a higher histological grade and higher Ki67 index than did the samples in group 5 but had a lower histological grade and lower Ki67 index than did the samples in group 1a (ratio ≥2.0, HER2 ≥6.0). CONCLUSION: Different categories of HER2 FISH test results have significant differences in clinicopathologic features. With no equivocal cases in 2018 HER2 guidelines, the clear division of HER2 status is helpful for making treatment recommendations about HER2 targeted therapy.

20.
BMC Public Health ; 19(1): 1507, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711447

RESUMO

BACKGROUND: The characteristics of recent HIV infections can provide the information about the dynamics of HIV transmission. Yunnan is one of the provinces hardest-hit by HIV-1 in China. To further understand the characteristics of the HIV-1 epidemic in Yunnan, we analyzed the prevalence of recent HIV-1 infections among newly diagnosed cases, identified the associated factors and explored the spatial distribution of recent HIV-1 infections. METHODS: Residual plasma samples from HIV-1 diagnostic tests were preserved. The associated information was collected from China HIV/AIDS case reporting system. Recent HIV-1 infections were estimated by combining the information about disease progression and BED- capture enzyme immunoassay (CEIA). The proportions of recent HIV-1 infections among newly diagnosed cases stratified by demographic characteristics were analyzed. The spatial clusters of recent HIV-1 infections were investigated by spatial scan statistics. RESULTS: Among 6119 HIV/AIDS cases were newly reported between January 2015 and June 2015 in Yunnan Province, 9.3% (570/6119) were estimated as recent infections. Female, aged below 25 years and homosexual contact were more associated with the higher proportion of recent HIV-1 infections. Among the different demographic sub-groups, men who have sex with men (MSM) aged < 25 years and ≥ 50 years had a higher chance of being diagnosed as recent infections, heterosexually infected men aged ≥25 years had a lower chance of being diagnosed as recent infections. In the sub-groups with different screening approaches, the highest proportion of recent infections (16.1%) was found among women diagnosed by testing during pregnancy and childbirth. In the sub-groups with different contact histories, the higher proportion of recent infections was found among the female cases having commercial heterosexual contacts (16.4%) and MSM (19.7%). The statistically significant spatial clusters of recent infections attributed to heterosexual contact, homosexual contact and intravenous drug injection were identified, respectively. CONCLUSIONS: The investigation of recent HIV infections among newly diagnosed cases supplements the routine HIV surveillance, and reveals the characteristics of ongoing HIV transmission. Our finding identified the potential sub-populations and geographic areas in need of services or improved interventions.

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