The Nelson mortality results were presented in September 2018. Four other randomized control trials (RCTs) were also reported the latest mortality outcomes in 2018 and 2019. We therefore conducted a meta-analysis to update the evidence and investigate the benefits and harms of low-dose computed tomography (LDCT) in lung cancer screening. Detailed electronic database searches were performed to identify reports of RCTs that comparing LDCT to any other type of lung cancer screening. Pooled risk ratios (RRs) were calculated using random effects models. We identified nine RCTs (n = 97,244 participants). In pooled analyses LDCT reduced lung cancer mortality (RR 0.83, 95% CI 0.76–0.90, I2 = 1%) but had no effect on all-cause mortality (RR 0.95, 95% CI 0.90–1.00). Trial sequential analysis (TSA) confirmed the results of our meta-analysis. Subgroup defined by high quality trials benefitted from LDCT screening in reducing lung cancer mortality (RR 0.82, 95% CI 0.73–0.91, I2 = 7%), whereas no benefit observed in other low quality RCTs. LDCT was associated with detection of a significantly higher number of early stage lung cancers than the control. No significant difference (RR 0.64, 95% CI 0.30–1.33) was found in mortality after invasive procedures between two groups. In meta-analysis based on sufficient evidence demonstrated by TSA suggests that LDCT screening is superiority over usual care in lung cancer survival. The benefit of LDCT is expected to be heavily influenced by the risk of lung cancer in the different target group (smoking status, Asian) being screened.

Studies have shown that elevated plasma levels of platelet-derived soluble TREM-like transcript-1 (sTLT-1) are associated with an unfavorable outcome in patients with septic shock. However, the underlying molecular mechanisms are not well defined. This research aimed to study the role of sTLT-1 in mediating immune dysfunction during the development of sepsis. Our study demonstrated that patients with septic shock have significantly higher plasma concentrations of sTLT-1, whereas sTLT-1 is not detectable in healthy subjects. Plasma concentrations of sTLT-1 were correlated with the degree of immunosuppressive parameters in monocytes from patients with septic shock. sTLT-1 can first activate monocytes by binding to the TLR4/MD2 complex but subsequently induce immunosuppressive phenotypes in monocytes. Blocking Abs against TLR4 and MD2 led to a significant decrease in sTLT-1–induced activation. Treatment with an anti–TLT-1 Ab also significantly reduces sTLT-1 binding to monocytes and proinflammatory cytokine secretion in a mouse model of endotoxemia. sTLT-1 acts as an endogenous damage-associated molecular pattern molecule, triggering the activation of monocytes through the TLR4/MD2 complex followed by sustained immune suppression. This process plays a crucial role in the development of sepsis-associated pathophysiology. Our findings outline, to our knowledge, a novel pathway whereby platelets counteract immune dynamics against infection through sTLT-1.

The cellular immune response for Mycobacterium tuberculosis (M. tuberculosis) infection remained incompletely understood. To uncover membrane proteins involved in this infection mechanism, an integrated approach consisting of an organic solvent-assisted membrane protein digestion, stable-isotope dimethyl labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used to comparatively profile the membrane protein expression of human dendritic cells upon heat-killed M. tuberculosis (HKTB) treatment. Organic solvent-assisted trypsin digestion coupled with stable-isotope labeling and LC-MS/MS analysis was applied to quantitatively analyze the membrane protein expression of THP-1 derived dendritic cells. We evaluated proteins that were upregulated in response to HKTB treatment, and applied STRING website database to analyze the correlations between these proteins. Of the investigated proteins, aminopeptidase N (CD13) was found to be largely expressed after HKTB treatment. By using confocal microscopy and flow cytometry, we found that membranous CD13 expression was upregulated and was capable of binding to live mycobacteria. Treatment dendritic cell with anti-CD13 antibody during M. tuberculosis infection enhanced the ability of T cell activation. Via proteomics data and STRING analysis, we demonstrated that the highly-expressed CD13 is also associated with proteins involved in the antigen presenting process, especially with CD1 proteins. Increasing expression of CD13 on dendritic cells while M. tuberculosis infection and enhancement of T cell activation after CD13 treated with anti-CD13 antibody indicates CD13 positively involved in the pathogenesis of M. tuberculosis.

Cancer cell–immune cell hybrids and cancer immunotherapy have attracted much attention in recent years. The design of efficient cell pairing and fusion chips for hybridoma generation has been, subsequently, a subject of great interest. Here, we report a three-layered integrated Microfluidic Flip-Chip (MFC) consisting of a thin through-hole membrane sandwiched between a mirrored array of microfluidic channels and saw-tooth shaped titanium electrodes on the glass. We discuss the design and operation of MFC and show its applicability for cell fusion. The proposed device combines passive hydrodynamic phenomenon and gravitational sedimentation, which allows the transportation and trapping of homotypic and heterotypic cells in large numbers with pairing efficiencies of 75~78% and fusion efficiencies of 73%. Additionally, we also report properties of fused cells from cell biology perspectives, including combined fluorescence-labeled intracellular materials from THP1 and A549, mixed cell morphology, and cell viability. The MFC can be tuned for pairing and fusion of cells with a similar protocol for different cell types. The MFC can be easily disconnected from the test setup for further analysis.

In an effort to improve the delivery of drugs to the lungs, various spacer devices have been developed to attach to metered-dose inhalers (MDIs). The aim of the study was to determine whether use of a small volume tube spacer with MDI is associated with better bronchodilatation. We assessed bronchodilatation by measuring forced expiratory volume in 1 second (FEV(1)) before and after inhalation of fenoterol 0.4 mg (2 puffs) delivered by using a MDI in four different ways: with or without a spacer alone or with a mouth rinse of 100 mL of water immediately after inhalation with or without a spacer. Results. A total of 303 patients who had a positive bronchodilator test were studied. There was no significant difference in the Delta FEV(1) (mL or %) with or without a spacer (MDI + spacer vs. MDI, mean +/- SD, 365.1 +/- 146.5 mL vs. 356.3 +/- 131.1 mL, p = 0.696; and 21.4 +/- 9.4% vs. 21.4 +/- 9.5%, p = 0.968, respectively). When patients rinsed their mouth after inhalation, bronchodilatation was significantly less in those using an MDI alone compared with MDI + spacer (302.6 +/- 116.5 mL vs. 367.6 +/- 128.3 mL, p = 0.002; and 18.0% +/- 7.9% vs. 21.7% +/- 9.5%, p = 0.013, respectively). When patients correctly use an MDI, addition of a spacer does not significantly improve bronchodilatation. However, if the mouth is rinsed after inhalation, a spacer does yield better bronchodilatation. Our results suggest that systemic effects from bronchodilator inhalation may not be negligible.