Etiology and characteristics of community-acquired pneumonia in an influenza epidemic period.

PURPOSE: The etiology of community-acquired pneumonia (CAP) in hospital patients is often ambiguous due to the limited pathogen detection. Lack of a microbiological diagnosis impairs precision treatment in CAP. METHODS: Specimens collected from the lower respiratory tract of 195 CAP patients, viruses were measured by the Single-plex real-time PCR assay and the conventional culture method was exploited for bacteria. RESULTS: Among the 195 patients, there were 46 (23.59%) pure bacterial infections, 20 (10.26%) yeast infections, 32 (16.41%) pure viral infections, 8 (4.10%) viral-yeast co-infections, and 17 (8.72%) viral-bacterial co-infections. The two most abundant bacteria were Acinetobacter baumannii and klebsiella pneumoniae, whereas the most common virus was influenza A. CONCLUSIONS: Non-influenza respiratory microorganisms frequently co-circulated during the epidemic peaks of influenza, which easily being ignored in CAP therapy. In patients with bacterial and viral co-infections, identifying the etiologic agent is crucial for patient's therapy.

Serum cytokines and clinical features in patients with fever and thrombocytopenia syndrome.

PURPOSE: To explore the clinical, microbiological and immunological features of patients with fever and thrombocytopenia. METHODS: Patients with unexplained fever and thrombocytopenia were enrolled. Viruses were detected using real-time PCR, and bacteria were measured by culturing methods. Serum cytokines, platelet antibody IgG (PA-IgG) and Helicobacter pylori (HP) were detected using ELISA. RESULTS: Pathogens were detected in 74.68% of patients, which included single fungal/viral/bacterial infection and multiple infection. The pathogens could not be unidentified in 25.32% of cases. Cytokines including Interleukin (IL)-6, IL-10, interferon-γ(IFN-γ), platelet activating factor (PAF) and PA-IgG were significantly higher in patients as compared to healthy controls (P < .01 or P < .05). Principal component analyses extracted four groups of parameters that have a strong positive predicting value, revealing that disease status evaluation would be more accurate if we combined the platelet parameters and inflammatory biomarkers. While event-free survival (EFS) that indicates the time of platelet elevated after therapy was the highest in patients with single bacterial or fungal infection, EFS was affected by the levels of cytokines and PA-IgG. CONCLUSIONS: Differences in immune function may be the main factors affecting the prognosis of patients with fever and thrombocytopenia, while treatment based on precise etiological diagnosis is important for therapeutic efficacy.

The role of cytokines and chemokines in the microenvironment of the blood-brain barrier in leukemia central nervous system metastasis.

AIM: Central nervous system (CNS) metastasis is a major obstacle in the treatment of leukemia, and the underlying mechanisms of leukemia CNS metastasis are not fully understood. The present study is an investigation of the role of the CNS microenvironment in leukemia CNS metastasis. METHODS: Analog blood-brain barrier (BBB) was set by coculturing human brain microvascular endothelial cells (HBMVECs) and leukemia cells (U937 and IL-60), as well as HBMVECs and sera from leukemia patients, in vitro. The permeability of the HBMVEC monolayer and the levels of tight junction proteins, cytokines and chemokines (C&Ckines) were measured. RESULTS: The permeability of HBMVECs increased when cocultured with leukemia sera. The expression of C&Ckines was significantly upregulated in HBMVECs cocultured with leukemia sera or leukemia cells, compared to the normal sera (P<0.05, respectively). Specifically, significantly higher levels of vascular endothelial growth factor A (VEGF-A) and matrix metalloprotease 9 (MMP-9) were found in HBMVECs and leukemia cells/sera coculturing systems. CONCLUSION: Both leukemia cells and the molecules in leukemia sera play an important role in leukemia CNS metastasis. VEGF-A and MMPs may be the main factors resulting in the degradation of the BBB and inducing the CNS migration of leukemia cells.

Th17 cytokine profiling of colorectal cancer patients with or without enterovirus 71 antigen expression.

OBJECT: Th17 cytokines have been identified in several types of human cancers. In this pilot study, the expression of Th17 cytokines profiling in enteroviruses 71 (EV71) associated colorectal cancer (CRC) were explored. METHODS: 66 patients with CRC were enrolled in this study; immune- histochemical analyses were performed on cancerous tissues and adjacent non- cancerous tissues of the patients. Serum Th17 cytokines of CRC patients and healthy controls were measured using a Luminex 200 analyzer. RESULTS: Cancerous tissues had more positive EV71 antigen expression than adjacent non- cancerous tissues. In TNM II-III CRC, 59.9% of cancerous tissues were observed to be EV71 positive; on the contrary, 65.2% of the adjacent non- cancerous epithelium was EV71 negative. In TNM I CRC, all adjacent non- cancerous epithelium was virus negative, but in TNM IV, half of adjacent non- cancerous tissues were virus positive. Serum IL-10 were significantly higher in CRC patients than in healthy controls, and IL-10 concentrations in the EV71 positive group were higher than those of the EV71 negative group, with the highest IL-10 levels being observed in CRC patients with strong positive group (P < 0.05). Similar results were found for IL-21 and IL-23. IL-17 levels were higher in CRC patients than in healthy controls, there was no significant difference in IL-17 between the viral positive and viral negative groups (P > 0.05). CONCLUSION: Persistent existing EV71 viral antigens in intestinal tissues are positively associated with TNM III/IV CRC. EV71 latent infection recruits Th17 cells in the colorectal tumor site, stimulating Th17 cytokine production that closely associated with CRC carcinogenesis.

The Clinical Significance of FilmArray Respiratory Panel in Diagnosing Community-Acquired Pneumonia.

AIM: FilmArray Respiratory Panel (FilmArray RP) test is an emerging diagnostic method in fast detecting multiple respiratory pathogens; the methodology and clinical significance of FilmArray RP in community-acquired pneumonia (CAP) diagnosis were evaluated in this study. METHODS: Specimens from 74 patients with CAP were analyzed and compared using FilmArray RP, traditional multiple PCR assay, bacterial (or fungal) culture, and serological detection. RESULTS: FilmArray RP and multiplex PCR showed 100% coincidence rate in detecting coronaviruses 229E, OC43, HKU1, and NL63, human metapneumovirus, influenza A and B, and parainfluenza viruses (PIV1, PIV2, and PIV4). There were 15 viral specimens tested as disagreement positive results. FilmArray RP had higher detection rate in detecting dual viral and Mycoplasma pneumoniae infection. The positive bacteria (or fungi) were found in 25 specimens. CONCLUSIONS: This study demonstrated the capability of FilmArray RP for simultaneous detection of broad-spectrum respiratory pathogens and potential use in facilitating better patient care.

Circulating microRNAs as a biomarker to predict therapy efficacy in hepatitis C patients with different genotypes.

BACKGROUND: Hepatitis C virus (HCV) genotype exerts a major influence on therapeutic response; however, the underlying mechanisms remain unclear. The aim of the study is to investigate the circulating microRNAs as the biomarkers to predict the response to therapy in chronic hepatitisC patients (HepC) with different genotypes. METHODS: HepC patients were separated into 4 groups by genotype, healthy individuals were enrolled as the control. microRNA-122 (miR-122), microRNA-155 (miR-155) and HCV RNA in serum and exosome were measured, associations between microRNAs, viral load and other conventional biomarkers were analyzed. RESULTS: Serum and exosomal HCV RNA in genotype 6a group was highest, followed by genotype 3a/2a, and in genotype 1b were the lowest. The significant correlations existed between exosomal HCV RNA and serum HCVRNA. MiR-122, both in serum (miR-122ser) and in exosome (miR-122exo), was higher in normal control than in HCV group. Specifically, miR-122exo were significantly higher in genotype 1b than other genotype groups (p < 0.05). On the contrary, miR-155exowas significantly lower in genotype 1b than in other groups (p < 0.05 for both). A strongly positive association was found between miR-122/155 and HCV viral load in patients with various genotypes. Higher miR-122ser at the start of therapy predicts a better outcome. CONCLUSIONS: Expression of miR-122/155 differ in each genotypes, miR-122ser could be independent factor affecting the therapy efficacy, which had higher diagnostic value in predicting HCV outcome.

Serum and exosomal miR-122 and miR-199a as a biomarker to predict therapeutic efficacy of hepatitis C patients.

MicroRNA (miRNA), which has been shown to correlate with liver functions, has been proposed as a new biomarker reflecting liver injury. The aim of the study was to investigate miRNA-122 (miR-122) and mir-RNA-199a (miR-199a) as a biomarker for predicting therapeutic efficacy in hepatitis C (HepC) patients. A total of 47 HepC 1b patients and 16 healthy subjects were enrolled in the study. Serum and exosomal mir-RNAs and other conventional biomarkers reflecting liver function were evaluated. The miR-122 levels in serum (miR-122ser ) and exosomes (miR-122exo ) were significantly lower in the Hepatitis C virus (HCV) genotype 1b patients than in the normal controls, but these levels were higher compared to the non-genotype 1b group. The mean miR-122ser level in the sustained virological response (SVR) group was significantly higher than that in the non-response (NR) group (P < 0.01), and the miR-122exo level in the SVR group was also higher than that in the NR group (P > 0.05), although this difference was not significant. miR-199a levels showed similar trends with the miR-122 levels in serum and exosomes. HCV RNAser was negatively correlated with the miR-122ser (r = -0.473, P = 0.004) and miR-122exo (r = -0.424, P = 0.009) levels. miR-122ser levels were positively associated with miR-199aser levels (r = 0.453, P = 0.002). Univariate and multivariate regression analyses reveal that the miR-122ser levels and ALT/AST ratio demonstrated a predictive value in evaluating patient outcomes. Serum miR-122 and miR-199a are potential biomarkers that reflect therapeutic efficacy.

Circulating tight junction proteins mirror blood-brain barrier integrity in leukaemia central nervous system metastasis.

The aim of this study was to evaluate the clinical significance of circulating tight junction (TJ) proteins as biomarkers reflecting of leukaemia central nervous system (CNS) metastasis. TJs [claudin5 (CLDN5), occludin (OCLN) and ZO-1] concentrations were measured in serum and cerebrospinal fluid (CSF) samples obtained from 45 leukaemia patients. Serum ZO-1 was significantly higher (p < 0.05), but CSF ZO-1 levels were not significantly higher in the CNS leukaemia (CNSL) compared to the non-CNSL. The CNSL patients also had a lower CLDN5/ZO1 ratio in both serum and CSF than in non-CNSL patients (p < 0.05). The TJ index was negatively associated with WBCCSF , ALBCSF and BBB values in leukaemia patients. Among all of the parameters studied, CLDN5CSF had the highest specificity in discriminating between CNSL and non-CNSL patients. Therefore, analysing serum and CSF levels of CLDN5, OCLN and the CLDN5/ZO1 ratio is valuable in evaluating the potential of leukaemia CNS metastasis. Copyright © 2016 John Wiley & Sons, Ltd.

Diagnostic value of platelet indices and bone marrow megakaryocytic parameters in immune thrombocytopenic purpura.

Platelet indices could mirror megakaryopoietic activity in immune thrombocytopenic purpura (ITP), but its specificity and sensitivity need to be studied. The diagnostic performance of platelet indices was analyzed by receiver-operating characteristic curves, and the probability of true positive (sensitivity) and true negative (specificity) in predicting ITP, myelodysplasia, or controls was determined. Mean platelet volume (MPV) was higher, whereas plateletcrit (PCT) was significantly lower in ITP than in myelodysplasia and controls. The platelet distribution width in ITP patients was lower than in myelodysplasia, but higher than in controls. Increased megakaryocytes were only observed in ITP. A strong positive correlation was found between MPV and quantities of granular megakaryocytes, whereas a negative relationship existed between MPV and platelet-form megakaryocytes. In receiver-operating characteristic analysis, MPV and PCT gave a sensitivity of 70.3% (89.8%) and specificity of 74.8% (84.7%) at a cutoff of 9.35 (0.085) in diagnosis of ITP. Combined parallel test of MPV and PCT increased the sensitivity to 97.5 with 64.1% specificity, whereas series test increased the specificity to 94.7 with 62.7% sensitivity. Our results suggest that MPV, PCT, and platelet distribution width represent megakaryopoietic activity in bone marrow and may be reliable markers in ITP diagnosis.