Search

CF is considered a rare disease among the non-Caucasian population. The clinical phenotypes and genotypic spectrum of Chinese CF patients are reported to be different from that observed in Caucasians[(1)](#ref-0001). Our patient carried compound heterozygous mutations which are not included in the Caucasian CFTR common mutation-screening panel and have not been reported yet. CFTR dysfunction causes a spectrum of diseases, with a range in the number of organs involved and varying disease severity. Typical phenotypic features of CF include respiratory diseases (bronchiectasis with persistent airway-based infection and inflammation), gastrointestinal diseases (meconium ileus (MI)), hepatobiliary manifestations (pancreatic insufficiency), and male infertility[(2)](#ref-0002). Our patient presented severe manifestations, namely colonic perforation, meconium thorax, severe pneumonia, diaphragmatic defects-caused marked diaphragm elevation and respiratory failure. It’s difficult to ascertain whether the diaphragmatic defects in our patient is related to CF. MI is often the first manifestation of CF and occurs in approximately 20% of CF patients. CF should therefore be high in the differential diagnosis of any infant presenting with MI[(3)](#ref-0003).

Since the discovery of ABO blood types, there has been mounting evidence of the association between blood types and infectious diseases. However, so far, there is rarely available research about the potential role of ABO blood types in haemorrhagic fever with renal syndrome (HFRS) infection. Our aim was to investigate the relationship between ABO blood types and the development of HFRS infection in Qingdao, China. We carried out a retrospective study enrolling 116 HFRS patients as the case group and 373 healthy subjects as the control group. ABO blood type distribution was analysed using the Chi-square test and logistic regression analysis. Results showed that the distribution of ABO blood types between the two groups was significantly different (X2 = 18.151, P < 0.05). Blood type B was less frequently observed [odds ratio (OR), 0.404; confidence interval (CI), 0.238–0.684; P < 0.01], while blood type AB was more frequently observed in the case group (OR, 2.548; CI, 1.427–4.549; P < 0.01). Since significantly more males were affected than females, we further analysed the data by gender as well as blood types and obtained consistent results for males. Our findings indicated that populations with blood type AB might be more prone to HFRS infection, whereas those with blood type B might be less susceptible to HFRS infection, which will help to make risk stratification in infection control.

Breast cancers with estrogen receptor (ER) expressions account for the majority of all clinical cases. Due to hormone therapy with tamoxifen, prognoses of patients with ER-positive breast cancer are significantly improved. However, endocrine resistance to tamoxifen is common and inevitable, leading to compromised efficacy of hormone therapy. Herein, we identify a crucial role of IL-33 in inducing endocrine resistance of breast cancer. IL-33 overexpression in breast cancer cells results in resistance to tamoxifen-induced tumor growth inhibition, while IL-33 knockdown corrects this problem. Mechanistically, IL-33 induces breast cancer stem cell properties evidenced by mammosphere formation and xenograft tumorigenesis, as well as expression of cancer stem cell genes including ALDH1A3, OCT4, NANOG and SOX2. In breast cancer patients, higher serum IL-33 levels portend advanced clinical stages, poorly differentiated cancer cells and tumor recurrence. IL-33 expression levels in patients' freshly isolated breast cancer cells predicts tamoxifen resistance and cancer stem cell features in individual patient. Collectively, IL-33 induces endocrine resistance of breast cancer by promoting cancer stem cell properties. These findings provide novel mechanisms connecting IL-33 with cancer pathogenesis and pinpoint IL-33 as a promising target for optimizing hormone therapy in clinical practice.

IL-33 is a member of IL-1 superfamily that drives production of Th2-related cytokines. Recently, accumulating evidence suggest an involvement of IL-33 in carcinogenesis. Herein, we determine a close correlation of IL-33 expression and cancer progress in patients with non-small-cell lung cancer (NSCLC). Overexpression of IL-33 by transfection with IL-33 expression vector enhances NSCLC outgrowth and metastasis, while genetic knockdown of IL-33 by transfection with IL-33 shRNA limits NSCLC progression. In consistent, IL-33 stimulation of NSCLC cells leads to robust NSCLC outgrowth and metastasis in vitro and in vivo. Mechanically, IL-33-triggered NSCLC progression relies on ST2 receptor and could be abrogated by ST2 blockade. IL-33/ST2 pathway up-regulates membrane glucose transporter 1 (GLUT1) on NSCLC cells, enhancing their glucose uptake and glycolysis. Accordingly, interfering GLUT1 expression dampens IL-33-enhanced glucose uptake and glycolysis in NSCLC cells, thereby abrogates IL-33-induced NSCLC outgrowth and metastasis. In essence, these findings derived from patients' NSCLC cells uncover a new function of IL-33 in NSCLC pathogenesis and identify GLUT1 as a novel target of IL-33 signaling. Block IL-33 is a promising therapeutic strategy to limit NSCLC glycolysis and tumor progression in clinical practice.

BACKGROUND Acute appendicitis is the most common surgical emergency in pediatrics. In this study, we aimed to evaluate the diagnostic value of D-dimer in differentiating between simple and other severe acute appendicitis in children combined with white blood cell (WBC) count, neutrophil percentage, and C-reactive protein (CRP). METHODS A retrospective study enrolled 327 consecutive patients who underwent appendectomy for acute appendicitis (aged 13 days to 14 years) in Qingdao Women & Children's Hospital from Jan 2013 to Dec 2014. WBC count, neutrophil percentage, CRP, and D-dimer levels were measured. Descriptive analyses, Student's t-test, and receiver operating characteristic (ROC) analyses were used to quantify the correlation between D-dimer level and the severity of appendicitis and to evaluate the differential diagnostic value of D-dimer combined with WBC count, neutrophil percentage and CRP between simple and other severe appendicitis. RESULTS Compared with simple appendicitis, WBC count, neutrophil percentage, CRP, and D-dimer levels were all significantly higher in other severe appendicitis (p < 0.01). Both CRP and D-dimer levels were positively correlated with the severity of disease. In differentiating between simple and other severe appendicitis, CRP (area under the ROC curve (AUC): 0.841) showed the highest sensitivity (80.7%) and the highest negative predictive value (NPV) (60.0%), while D-dimer (AUC: 0.793) showed the highest specificity (90.0%) and the highest positive predictive value (PPV) (94.9%). Combined CRP and D-dimer had a sensitivity, specificity, PPV, NPV, and accuracy of 87.5%, 94.6%, 97.8%, 72.9%, and 89.4%, respectively. CONCLUSIONS CRP and D-dimer levels are positively correlated with the severity of acute appendicitis in children. Combined CRP and D-dimer are identified as suitable diagnostic markers for differentiating between simple and other severe appendicitis, which will provide important guidance for clinicians to determine the follow-up management of acute appendicitis.

Background Autoimmune hemolytic anemia (AIHA), a life-threatening anemia with rapid onset, is caused by autoantibody directed to self red blood cells (RBCs). Currently, mechanisms underlying AIHA pathogenesis are largely undefined. Here we explored the correlation of IL-33 with AIHA disease activity and evaluated IL-33 based therapeutics in AIHA treatment. Methods Thirty patients diagnosed with AIHA of warm-type autoantibodies without treatment were enrolled and followed up for 6 months. Levels of cytokines including IL-33, IL-4, IL-6 and IL-13 was determined with ELISA. AIHA disease activity was presented by levels of reticulocyte count, hemoglobin and lactate dehydrogenase. Serum RBC-bound IgG autoantibody was detected using anti-IgG antibody with flow cytometry. To evaluate the effect of IL-33 blockade on AIHA development, groups of B6 mice were immunized with rat RBCs plus recombinant IL-33 protein or IL-33 neutralizing antibody respectively and detected for levels of anti-RBC antibody, frequency of reticulocytes and destruction of transfused syngeneic mouse RBCs. Results Serum level of IL-33 was higher in AIHA patients compared with healthy individuals. Of interest, serum IL-33 was positively correlated with AIHA disease activity and sensitive to their changes in AIHA patients under clinical management. Mechanistically, IL-33 could promote the production of anti-RBC autoantibody. Serum IL-33 was closely associated with serum anti-RBC autoantibody and sensitive to their changes in AIHA patients. Accordingly, blockade of IL-33 interfered with AIHA incidence and ameliorated disease activity. Vice vasa, enforced IL-33 promoted AIHA incidence and disease activity. Conclusions IL-33 was a potential biomarker for monitoring disease activity and therapeutic response in AIHA patients. Targeting IL-33 was a promising strategy for controlling autoantibody production in AIHA patients. Electronic supplementary material The online version of this article (doi:10.1186/s12967-015-0745-0) contains supplementary material, which is available to authorized users.

Additional file 1: Figures. Gating strategy for anti-RBC antibody analysis, serum levels of sST2 in AIHA patients, Th2 cytokines in AIHA mice co-injected with IL-33 protein or IL-33 neutralizing antibody, B cell response to IL-33 stimulation or IL-33 blockade, and effect of IL-6 on IL-33-mediated autoantibody production were presented.