Objective Tracheobronchial foreign bodies (FBs) are frequently present in adults. This study reports our experience with the managements of FB and FB-related complications using flexible bronchoscopy. Methods We retrospectively reviewed the adult patients with FBs treated between 2001 and 2011 in China. The demographic and endoscopic data were collected and analyzed. Results A total of 200 adult patients (136 men and 64 women) with an average age of 51 years were analyzed. The most common FBs included bones (51.0%), nut shells (15.0%), food boluses (7.0%), plastic toys or pen caps (6.5%). After FB aspiration occurred, only 11.0% were diagnosed within three days, while more than half of the patients (58.0%) delayed the diagnosis by more than one month. The incidence of FB-related complications was 79.5%, including granulation formation (76.5%), obstructive pneumonia (22.0%), hemorrhage (14.5%), atelectasis (10.0%) and endobronchial stenotic scarring (8.0%). In 96.5% of the patients, the FBs were successfully removed under flexible bronchoscopy. A total of 53 out of the 153 patients with granulation (34.6%) were managed by argon plasma coagulation (APC) or cryotherapy; two out of the sixteen patients with endobronchial stenotic scars were treated by balloon dilation under flexible bronchoscopy. Conclusion A high incidence of FB-related complications occurs, likely as a result of the long delay between aspiration and diagnosis, a proportion of which require endoscopic intervention. The removal of FBs under flexible bronchoscopy has a high success rate and therefore should be recommended for adults.

Background: Human natural killer (NK) cells are the key contributors of innate immune response and the effector functions of these cells are enhanced by cytokines such as interleukine 2 (IL2). We utilized genome-wide transcriptional profiling to identify gene expression signatures and pathways in resting and IL2 activated NK cell isolated from peripheral blood of healthy donors.

Usher syndrome type III is an autosomal recessive disorder characterized by progressive sensorineural hearing loss, vestibular dysfunction, and retinitis pigmentosa. The disease gene was localized to 3q25 and recently was identified by positional cloning. In the present study, we have revised the structure of the USH3 gene, including a new translation start site, 5' untranslated region, and a transcript encoding a 232-amino acid protein. The mature form of the protein is predicted to contain three transmembrane domains and 204 residues. We have found four new disease-causing mutations, including one that appears to be relatively common in the Ashkenazi Jewish population. We have also identified mouse (chromosome 3) and rat (chromosome 2) orthologues, as well as two human paralogues on chromosomes 4 and 10.

Progression of follicular lymphoma (FL) to a higher-grade lymphoma occurs in 25% to 60% of cases and frequently indicates a poor prognosis. The transformation is accompanied by alteration in morphologic features and clinical behaviors. Herein, we report a case of FL occurring in a 59-year-old woman with the development of a precursor B-cell lymphoblastic lymphoma (PBC-LBL) during a 6-month period. Both lymphomas had identical bcl-2 and immunoglobulin heavy-chain gene breakpoints as assessed by polymerase chain reaction amplification and direct sequencing, indicating that the 2 tumors originated from a common precursor B-cell clone or the PBC-LBL arose from clonal evolution of its preceding FL and "dedifferentiated" into a lymphoblastic stage. Immunohistochemical studies revealed that both lymphomas displayed typical phenotypic characteristics. A c-myc gene translocation was observed in the PBC-LBL but not the FL by fluorescence in situ hybridization. The c-myc translocation is also reported in similar cases in the literature and likely is crucial in the pathogenesis of the PBC-LBL.

Background:Anti-PD-1/PD-L1 antibody therapy is a promising clinical treatment for nonsmall-cell lung cancer (NSCLC). However, whether anti-PD-1/PD-L1 antibody therapy can provide added benefits for heavily pretreated patients with advanced NSCLC and whether the efficacy of anti-PD-1/PD-L1 antibody therapy relates to the tumor PD-L1 expression level remain controversial. Thus, this meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 antibody therapy for pretreated patients with advanced NSCLC.Methods:Randomized clinical trials were retrieved by searching the PubMed, EMBASE, ASCO meeting abstract, clinicaltrial.gov, and Cochrane library databases. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios for the overall response rate and adverse events (AEs) were calculated by STATA software.Results:Three randomized clinical trials involving 1141 pretreated patients with advanced NSCLC were included. These trials all compared the efficacy and safety of anti-PD-1/PD-L1 antibodies (nivolumab and MPDL3280A) with docetaxel. The results suggested that, for all patients, anti-PD-1/PD-L1 therapy could acquire a greater overall response (odds ratio = 1.50, 95% CI: 1.08–2.07, P = 0.015, P for heterogeneity [Ph] = 0.620) and longer OS (HR = 0.71, 95% CI: 0.61–0.81, P < 0.001, Ph = 0.361) than docetaxel, but not PFS (HR = 0.83, 95% CI: 0.65–1.06, P = 0.134; Ph = 0.031). Subgroup analyses according to the tumor PD-L1 expression level showed that anti-PD-1/PD-L1 therapy could significantly improve both OS and PFS in patients with high expressions of PD-L1, but not in those with low expressions. Generally, the rates of grade 3 or 4 AEs of anti-PD-1/PD-L1 therapy were significantly lower than that of docetaxel. However, the risks of pneumonitis and hypothyroidism were significantly higher.Conclusion:Anti-PD-1/PD-L1 antibody therapy may significantly improve the outcomes for pretreated advanced NSCLC patients, with a better safety profile than docetaxel.

A group of genes are highly expressed in normal germinal center (GC) B cells and GC B-cell-derived malignancies based on cDNA microarray analysis. Two new genes, GCET1 (germinal center B-cell expressed transcript 1) and GCET2, were cloned from selected expressed sequence tags (IMAGE clone 1334260 and 814622, respectively). GCET1 is located on chromosome 14q32 and has four splicing isoforms, of which the longest one is 1787 bp and encodes a 435-amino acid protein. GCET2 is located on 3q13.13, and the cloned fragment is 3270 bp, which encodes a protein of 178 amino acids. Blast search showed that GCET1 has a highly conserved serine proteinase inhibitor (SERPIN) domain and is located on a chromosomal locus containing seven other SERPIN family members. GCET2 is a likely homologue of the mouse gene M17, a GC-expressed transcript. Analysis of the GCET2 protein sequence indicated that it may be involved in signal transduction in the cytoplasm. Northern blot and real-time polymerase chain reaction analyses confirmed that GCET1 is highly restricted to normal GC B cells and GCB-cell-derived cell lines. Although GCET2 is also a useful marker for normal and neoplastic GC B cells, it has a wider range of expression including immature B and T cells. Real-time polymerase chain reaction assay showed that both GCET1 and GCET2 are preferentially expressed in follicular lymphoma and diffuse large B-cell lymphoma with GC B-cell differentiation, confirming previous microarray gene expression analysis, but neither one is entirely specific. Multiple markers are necessary to differentiate the GCB from the activated B-cell type of diffuse large B-cell lymphoma with a high degree of accuracy.

Summary Chromosome abnormalities influence prognosis and tumour progression in B‐cell Chronic Lymphocytic Leukaemia (CLL). This study sought to determine whether these different disease subgroups were associated with unique gene expression patterns. Thirty‐four cases of CLL were screened for the 11q23, 13q14, 17p13 deletions, and trisomy 12 by fluorescence in situ hybridization (FISH). Expression of 205 cell signalling and apoptosis genes were compared by cDNA array among cases with different chromosome abnormalities. A majority of the statistically differentially expressed genes were present in the 11q23 deletion group by hierarchical clustering. CDC2, a serine/threonine kinase, was overexpressed in the 11q23 deletion group (P = 0·0004) and confirmed by TaqmanTM real‐time polymerase chain reaction. Several other genes associated with cell signalling were overexpressed in the 11q23 deletion group. A strong overall correlation existed between the presence of different chromosome abnormalities and a number of prognostic factors including immunoglobulin heavy chain variable region mutation status (P = 0·011), time to treatment (P = 0·025) and lymphocyte doubling time (P = 0·034). This study confirmed the prognostic impact of chromosome abnormalities identified by FISH in CLL, particularly the 11q23 deletion and trisomy 12. In addition, the 11q23 deletion group was associated with a unique gene expression pattern involving cell signalling and apoptosis genes.

Mutations in RAD51 gene are believed to be associated with elevated breast cancer risk. However, several case-control studies focusing on the association between RAD51 135G>C and breast cancer risk failed to achieve consensus. To clarify the effect of RAD51 135G>C polymorphism on breast cancer, a meta-analysis was performed. By searching PubMed and EMBASE, a total of 14 case-control studies, containing 12,183 cases and 10,183 controls, were included. The strength of association between RAD51 135G>C polymorphism and breast cancer risk was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95% CI). When all the eligible studies were pooled into the meta-analysis, an elevated cancer risk was revealed in additive model (OR, 1.34; 95% CI, 1.01-1.78; P = 0.044) and recessive model (OR, 1.37; 95% CI, 1.03-1.82; P = 0.032). In subgroup analyses by ethnicity, BRCA1/2 mutation status, and family history, a significant association was found only among BRCA2 mutation carriers (additive model: OR, 4.92; 95% CI, 1.11-21.83; P = 0.036; recessive model: OR, 4.88; 95% CI, 1.10-21.67; P = 0.037). Sensitivity analysis did not perturb the results. In conclusion, this meta-analysis suggests that RAD51 variant 135C homozygote is associated with elevated breast cancer risk among BRCA2 mutation carriers.