Frequency ofT-cell FoxP3＋ Treg and CD4＋/CD8＋ PD-1 expression is related to HBeAg seroconversion in hepatitis B patients on pegylated interferon

Background Host immune responses against hepatitis B virus （HBV） induced by antiviral therapy play a crucial role in viral clearance. To further investigate the immune mechanisms underlying the differences between respondents and non-respondents, we analyzed myeloid dendritic cells （mDCs）, plasmacytoid dendritic cells （pDCs）, FoxP3＋ regulatory T cells （FoxP3＋ Treg） and programmed death 1 （PD-1） expression in CD4＋/CD8＋ T cells in chronic hepatitis B patients undergoing pegylated interferon （PeglFN）α-2b treatment. Methods Patients received PeglFNα-2b for 24 or 48 weeks, with follow-up at 24 weeks. The frequencies of mDCs, pDCs, FoxP3＋ Treg, and PD-1 expression by CD4＋/CD8＋ T cells were evaluated by flow cytometry at baseline, weeks 4 and 12, end of treatment, and follow-up （12/24 weeks）. Results In HBeAg seroconverters （respondents）, the mDC relative frequency decreased at week 4 and then rebounded at week 12. The pDC relative frequency decreased consistently. In non-HBeAg seroconverters （non-respondents）, both mDC and pDC frequencies decreased slightly. The FoxP3＋ Treg relative frequency decreased during treatment and remained low during follow-up in respondents, while in non-respondents it decreased slightly during therapy but rebounded after discontinuation. In patients with HBeAg 〈17.55 PEI-U/ml at week 12 and 〈8.52 PEI-U/ml at week 24, the FoxP3＋ Treg frequency decreased during treatment and at follow-up. In respondents, CD4~PD-1 and CD8＋PD-1 levels decreased at week 4 and remained low at week 12. In non-respondents, PD-1 expression decreased at week 4 but rebounded at week 12. Conclusions The results indicate that the dynamic changes in DCs, FoxP3＋ Treg frequency, and PD-1 expression by CD4＋ and CD8＋ T cells exhibit different trends in HBeAg and non-HBeAg seroconversion patients. During PeglFNa-2b treatment of chronic hepatitis B patients, these changes may be of predictive value for HBeAg seroconversion. HBsAg and HBeAg levels are related to FoxP3＋ Treg frequency.

Completely thoracoscopic lobectomy for the surgical management of bronchiectasis

Background The feasibility of completing a Iobectomy by completely video-assisted thoracoscopic surgery （cVATS） in the management of bronchiectasis is unclear. By retrospectively comparing the outcomes from the Iobectomies that used thoracotomy vs. cVATS, we determined the appropriateness of the minimally invasive cVATS approach in the management of bronchiectasis. Methods Between June 2001 and October 2010, 60 patients with bronchiectasis underwent surgery, of which 56 Iobectomies were performed. All Iobectomies were carried out by either thoracotomy or cVATS approach. Pulmonary vessels and bronchi were manipulated by ligation or stapler in the thoracotomy group, while they were dissected by endo-cutters in the cVATS group. Results There were 21 patients in the thoracotomy group and 35 patients in the cVATS group. Two cVATS patients （5.7%） converted. The difference in operation time, chest tube duration, lengths of hospitalization, and morbidity were not significantly different between the two groups （P 〉0.05）. The blood loss was less in the cVATS group （P=0.015）. A total of 52.4% and 62.9% of patients were postoperatively asymptomatic in the thoracotomy and cVATS groups respectively, and symptomatic improvement was obtained in 38.1% patients by thoracotomy vs. 31.4% patients by cVATS. Conclusion cVATS Iobectomy is safe and effective for the management of bronchiectasis, especially for the patients with localized lesions.

Programmed cell death 5 correlates with disease activity and interleukin-17 in serum and synovial fluid of rheumatoid arthritis patients

Background Programmed cell death 5 （PDCD5） is a novel apoptotic regulatory gene that promotes apoptosis in various tumor cells. Studies have shown that PDCD5 accelerates the apoptosis of synoviocytes in vitro, implying a potential role in rheumatoid arthritis （RA） pathogenesis. This study examined the expression of PDCD5 in serum and synovial fluid of RA patients, its effect on the expression of inflammatory cytokine, interleukin-17 （IL-17）, and the assessment of disease activity in RA. Methods PDCD5 and IL-17 levels in serum and synovial fluid from 18 patients with RA and 22 patients with osteoarthritis （OA） were detected using enzyme-linked immunosorbent assay （ELISA）. Concentrations of serum PDCD5 in 40 healthy people were also detected as controls. As disease activity indices, C-reactive protein （CRP）, erythrocyte sedimentation rate （ESR）, rheumatoid factor （RF）, and X-ray grading scale were also evaluated. Results Serum and synovial fluid PDCD5 levels in RA patients were significantly higher than those in OA and healthy controls. Serum PDCD5 level was inversely correlated to CRP and ESR, and was significantly higher in the RF negative group than in the positive group. PDCD5 level was also negatively correlated with IL-17 levels both in serum and synovial fluid of RA patients. However, differences in synovial fluid PDCD5 level from RA patients at different Larsen stages were not detectable. Conclusions PDCD5 affects RA pathogenesis. Insufficient apoptosis of fibroblast-like synoviocytes and inflammatory cells in RA could increase the expression of PDCD5 protein. As PDCD5 levels correlated negatively with disease activity indices and IL-17 level, PDCD5 could become a target in the diagnosis and treatment of RA.

Change of CMTM7 expression, a potential tumor suppressor, is associated with poor clinical outcome in human non-small cell lung cancer

Background CKLF-like MARVEL transmembrane domain-containing 7 （CMTM7） located at 3p22.3,is a frequent deletion site and a tumor suppressor gene （TSG） locus in many cancer,which suggests CMTM7 may be a potential TSG.The aim of this study was to investigate the correlations of CMTM7 expression and survival rate in patients with non-small-cell lung cancer （NSCLC）.Methods Surgical specimens of 180 cases with pathologically confirmed NSCLC were grouped into 18 tissue microarray slides.CMTM7 expression in these specimens were detected by immunohistochemistry staining and representative cases were confirmed by Western blotting.Univariate and multivariate analyses were performed to identify the association of CMTM7 expression with pathological features and survival of patients with NSCLC.Results A total of 78.9％ of the 180 patients had variations of CMTM7 protein expression,either up-regulated or downregulated.Univariate analysis showed that the patients＇ survival rate after surgery was highly correlated with CMTM7 expression （P=0.0091）.In addition,prognostic factors were examined by multivariate Cox regression analysis,and results suggested that CMTM7 expression was a unique prognostic factor in NSCLC survival.Conclusions The CMTM7 expression may be related to survival of patients with NSCLC and a unique prognostic factor.CMTM7 may play an important role in NSCLC development.

Effect of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on identifing biomarkers of endometriosis

Background Endometriosis is a common gynecological disease. This study aimed to screen proteins that were expressed differently in patients with endometriosis versus normal controls using proteomic techniques, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry （SELDI-TOF-MS）.Methods Protein chip SELDI-TOF-MS combines the advantages of microarray and mass spectrometry, and can screen latent markers in sera of patients with endometriosis. Serum samples from patients and normal volunteers were analyzed by SELDI-TOF-MS. Results After comparing the serum protein spectra of 36 patients with 24 normal controls, 24 differently expressed potential biomarkers （P 〈0.01） were identified. Using Biomarker Pattern software, we established a tree model of the 60 serum protein spectra. When using the three bJomarkers to classify the samples, the sensitivity for diagnosing endometriosis was 91.7%, specificity was 95.8%, and coincidence rate was 93.3%. Then we used serum samples from 12 patients and 8 normal controls to validate the tree model and report the sensitivity for diagnosing endometriosis was 91.7%, specificity was 75%, and coincidence rate was 85%. Conclusions SELDI-TOF-MS may be a useful tool in high-risk population screening for endometriosis. The identification and application of the biomarkers need to further study.

Pretreatment with interleukin-33 reduces warm hepatic ischemia/ reperfusion injury in mice

Background Interleukin （IL）-33 is a recently identified member of the IL-1 family that binds to the receptor, ST2L. This study examined IL-33 production in mouse liver and investigated its role in hepatic ischemia/reperfusion （I/R） injury. Methods Male BALB/c mice （（22＋3） g） were subjected to 90 minutes partial hepatic ischemia, followed by 6 hours reperfusion. First, mice were randomized into two groups： control group （laparotomy only, without blocking blood supply） and ischemia model group. IL-33 mRNA and serum protein levels were measured at 30, 60, 90 minutes after ischemia and 2 and 6 hours after reperfusion. Second, mice were randomized into four groups： control, model （injection of rabbit IgG polyclonal antibody）, recombinant IL-33 intervention and anti-ST2L antibody intervention group. Mice were sacrificed 6 hours after reperfusion. Liver pathology was observed via transmission electron microscopy. Serum aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, IL-4, IL-5, IL-13, interferon-y （IFN-y） and tumor necrosis factor-a （TNF-a） levels were measured. Results Levels of IL-33 mRNA and protein did not change during ischemia （P 〉0.05） but increased significantly during reperfusion （P 〈0.05）. After reperfusion for 6 hours, serum levels of ALT, AST, IL-4, IL-5, IL-13, IFN-~ and TNF-a were significantly increased （P 〈0.05）, and hepatocellular ultrastructure was damaged. Pretreatment with IL-33 attenuated severity of liver damage compared with controls, but pretreatment with anti-ST2L antibody increased severity. Serum levels of IL-4, IL-5 and IL-13 protein increased whereas IFN-y decreased following IL-33 pretreatment. Pretreatment with anti-ST2L antibody significantly decreased serum IL-4, IL-5, IL-13 levels and increased serum IFN-r levels compared with controls （P 〈0.05）. There was no change in the level of TNF-a. Conclusion IL-33 is produced systematically and locally in liver during I/R injury. Pretreatment with IL-33 is therapeutic for hepatic I/R injury, possibly via inducing a Thl to Th2 shift.

Relationship among symptoms, mucosal injury, and acid exposure in gastroesophageal reflux disease

Background Symptoms,endoscopy,and pH monitoring form the basis of diagnosis of gastroesophageal reflux disease （GERD）.Their relationship was meaningful for primary care physicians,but still unclear.Our research aimed to compare questionnaire,endoscopy,and pH monitoring and to analyze their correlations.Methods Three hundred patients who underwent the Reflux Disease Questionnaire （RDQ）,endoscopy,and esophageal 24-hour pH monitoring from March 2007 to December 2010 in Peking University People＇s Hospital were enrolled.We analyzed the characteristics of different investigations and their relationships.Results Male （OR for mild reflux esophagitis （RE） =2.433,severe RE =8.386）,body mass index （BMI） （OR for mild RE =1.222,severe RE =1.297）,and hernia （OR for mild RE =6.059,severe RE =17.547）,were found to be the risk factors for RE; age （OR=1.074） was correlated with severe RE.The consistency of questionnaire,endoscopy,and pH monitoring was poor：RDQ did not agree well with pH monitoring （K=0.061）,nor with endoscopy （K=0.044）; pH monitoring did not agree well with endoscopy （K=0.316）.However,the severity of mucosa injury in RE was associated with pathological acid exposure （PAE）：reflux episodes of ＞5 minutes （P=0.035）,the percentage time pH ＜4 （P=0.017）,and the DeMeester score （P=0.016） increased significantly in patients with severe RE.Chest pain had poor relationship with RE or PAE.Conclusions Male,age,BMI,and hernia were probably risk factors for esophagitis.RDQ,endoscopy,and pH monitoring have their own focus and reinforce each other in diagnosis.Of the GERD symptoms,chest pain had negative correlation with RE or PAE.

Detection and functional annotation of misregulated microRNAs in the brain of the Ts65Dn mouse model of Down syndrome

Background Brain hypoplasia and mental retardation in Down syndrome （DS） can be attributed to a severe and selective disruption of neurogenesis. Secondary disruption of the transcriptome, as well as primary gene dosage imbalance, is responsible for the phenotype. MicroRNA （miRNA） expression is relatively abundant in brain tissue. Perturbed miRNA expression might contribute to the cellular events underlying the pathology in DS. Methods MiRNA expression profiles in the cerebrum of Ts65Dn mice, a DS model, were examined with a real-time RT-PCR array. MiRNA target gene expression was detected by real-time quantitative PCR and Western blotting. Based on the prediction of their cerebrum-specific targets, the functions of the misregulated miRNAs were annotated by Gene Ontology （GO） enrichment analysis. Results A total of 342 miRNAs were examined. Among them, 20 miRNAs showed decreased expression in the brains of Ts65Dn mice, and some of these belonged to the same family. Two known targets of the miR-200 family, Lfng and Zeb2, were specifically selected to compare their expression in the cerebrum of Ts65Dn mice with those of euploids. However, no significant difference was found in terms of mRNA and protein expression levels of these genes. By enrichment analysis of the cerebrum-specific targets of each miRNA, we found that 15 of the differential miRNAs could significantly affect target genes that were enriched in the GO biological processes related to nervous system development. Conclusion Perturbed expression of multiple functionally cooperative miRNAs contributes to the cellular events underlying the pathogenesis of DS.

Inhaled unfractionated heparin improves abnormalities of alveolar coagulation, fibrinolysis and inflammation in endotoxemia-induced lung injury rats

Background Acute lung injury/acute respiratory distress syndrome presents with not only local inflammation, but also pulmonary coagulopathy which is characterized by an alveolar procoagulant response, anticoagulant inhibition, fibrinolytic supression and fibrin deposition. We thus had hypothesized that if aerosolized unfractionated heparin was inhaled into alveolar spaces, it could block the procoagulant tendency, lessen depletion of coagulation factors, and even influence the inflammatory response. We also assessed the effects of different administration regimens of heparin. Methods Male Wistar rats were given inhaled heparin starting 30 minutes before （prophylactic heparin） or 2 hours after （therapeutic heparin） intravenous lipopolysaccharide （LPS） was administered at 6-hour intervals; control groups received inhaled normal saline with or without being exposed to LPS. Thrombin-antithrombin complexes, activated protein C, tissue type and urokinase type plasminogen activators （t-PA/u-PA）, plasminogen activator inhibitor-1 （PAl-l）, tumor necrosis factor-a, interleukin-6 in bronchoalveolar lavage, and lung tissue myeloperoxidase activity, and histology score were measured at three time-points. PAI-1/（t-PA ＋ u-PA） was calculated based on the before-mentioned parameters. Statistical analysis was made using one-way analysis of variance （ANOVA） with post hoc test or Student＇s t test in the case of heterogeneity of variance. Results An alveolar procoagulant reaction, depressed fibrinolysis, and inflammatory response occurred in endotoxemia-induced lung injury. Local prophylactic application of heparin attenuated coagulation and early inflammation, promoted fibrinolysis, and reduced the histology score. Therapeutic application of heparin had similar, but weaker effects. Conclusions Intrapulmonary application of unfractionated heparin by inhalation might inhibit alveolar procoagulant reaction and the early inflammatory response, promote fibrinolysis, and alleviate pulmonary pathology in endotoxemia-induced lung injury rats. Administration of heparin before LPS challenge was more efficacious.

Positioning study of cervical vertebra pedicle axial line projective point by computed tomography image reconstruction

Background Safe placement of the screws is a critical aspect of trans-pedicle internal fixation, and little information on in vivo morphology of the cervical vertebrae pedicle measured with imaging methods is available. The aim of this study was to measure the dimensions of cervical vertebrae C3 to C7 and provide screw length, screw diameter and tilt angle for clinical cervical vertebra trans-pedicle internal fixation. Methods Thirty Chinese men and women underwent high-speed spiral computed tomography measurements to obtain data for C3 to C7, and the morphology of the cervical vertebra pedicles was reconstructed. Results Reconstructed computer tomography image data revealed that： （1） pedicle sponge width increased incrementally from C3 to C7, （2） pedicle depth was similar for C3 to C7, （3） pedicle angle decreased incrementally from 47.20~ to 33.76~ for＇ C3 to C7, and （4） pedicle point to midline distance was similar for C3 to C7. There were no statistical differences in morphological data between the right and the left side. Men had statistically larger values than women for all morphological parameters. Conclusions Reconstructed computed tomography images can provide useful data for clinical cervical vertebra trans-pedicle internal fixation. The individual measurement of cervical vertebra pedicles is recommended for safe placement of trans-vertebra pedicle screws.

Determinants for inadequate glycaemic control in Chinese patients with mild-to-moderate type 2 diabetes on oral antidiabetic drugs alone

Background Prevalence of inadequate glycaemic control among patients with type 2 diabetes mellitus （T2DM） remains high. We assessed glycaemic control in the real-life practice among people with T2DM in metropolises in China who were treated with oral antidiabetic drugs （OAD） alone and to determine factors associated with inadequate glycaemic control in this population. Methods An observational, cross-sectional multicentre study was conducted in 16 metropolitan medical centers. People with T2DM who had been followed-up before the index visit which occurred from January to September 2007 were included in the study. All subjects were 〉30 years of age at the time of T2DM diagnosis and had received monotherapy or combination therapy of OAD for at least 6 months. Demographic and clinical data were collected from medical records. The main study outcome was the inadequate glucose control rate, which was calculated by the proportion of patients with haemoglobin Alc （HbAlc） 〉6.5% detected on the index visit. Results In this cohort of 455 patients with T2DM whose mean age was 60.6 years and mean disease duration was 6.1 years, 45.5% had inadequate glycaemic control. The mean （SD） HbA1c was 6.7% （1.3）. Multivariate Logistic regression showed that physical inactivity, disease duration 〉10 years, body mass index （BMI） ≥24 kg/m2, low homeostasis model assessment of β-cell function （HOMA-13） index, less frequency of medical visit and hypertriglyceridaemia were independent determinants of inadequate glycaemic control. Higher incidence of self-reported hypoglycemia experience （47.1% vs. 34.8%, P=0.008） and more fear of hypoglycemia quantified by Worry subscale of the Hypoglycaemia Fear Survey （HFS） II were happened in subjects with good glycemic control. Conclusion Approximately one half of these outpatients with T2DM from the metropolitan medical centers in China had inadequate glycaemic control treated with OAD alone, which raises the need for more effective educational and therapeutic approaches on management of hypertriglycemia, enhancing physical exercise and weight control, and at the same time. Iowerina the hvooalvcemic risk and diminishina the hvooalvcemic fear of oatients.