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Pneumocystis jiroveci pneumonia (PCP) is frequently reported in lymphoma patients treated with rituximab-contained regimens. There is a trend toward a difference in PCP risk between bi- and tri-weekly regimens. The aims of this systemic review and meta-analysis were to estimate the risk for PCP in these patients, compare the impact of different regimens on the risk, and evaluate the efficacy of prophylaxis. The cohort studies with incept up to January 2014 were retrieved from the Cochrane Library, Medline, Embase, and Web of Science databases. Studies that compared the incidence of PCP in patients with and without rituximab treatment were conducted. Studies that reported the results of prophylaxis were concentrated to evaluate the efficacy of prophylaxis. Fixed effect Mantel-Haenszel model was chosen as the main analysis method. Funnel plots were examined to estimate the potential selection bias. Egger's test and Begg's test were used for the determination of possible small study bias. Eleven cohort studies that met the inclusion criteria were finally included. Results indicated that rituximab was associated with a significantly increased risk for PCP (28/942 vs 5/977; risk ratio: 3.65; 95% confidence interval 1.65 to 8.07; P=0.001), and no heterogeneity existed between different studies (I2=0%). Little significant difference in PCP risk was found between bi-weekly and tri-weekly regimens (risk ratio: 3.11; 95% confidence interval 0.92 to 10.52, P=0.068). PCP risk was inversely associated with prophylaxis in patients treated with rituximab (0/222 vs 26/986; risk ratio: 0.28; 95% confidence interval 0.09 to 0.94; P=0.039). In conclusion, PCP risk was increased significantly in lymphoma patients subjected to rituximab-contained chemotherapies. Difference in PCP risk between bi-weekly and tri-weekly regimens was not significant. Additionally, prophylaxis was dramatically effective in preventing PCP in rituximab-received lymphoma patients, suggesting that rituximab should be recommended for these patients.

Three-dimensional ghost imaging LiDAR via sparsity constraint (3D GISC LiDAR), as a staring imaging method, can obtain both the range information and spatial distribution of a remote target with a single-pixel time-resolved detector. However, previous demonstrations mainly focused on the relatively static scene in visible light. Here we propose an airborne near infrared 3D GISC LiDAR system and airborne high-resolution imaging is implemented. Experimental results show that an image with 0.48 m horizontal resolution as well as 0.5 m range resolution at approximately 1.04 km height can be achieved. Some considerations on the improvement of this LiDAR system are also discussed.

Toll-like receptors (TLRs) are innate pattern recognition receptors that play a critical role in allergic inflammation, yet their contribution to autophagy in asthma remains poorly defined. Here, we investigate the role of Toll-like receptor 2 (TLR2) in phosphoinositide 3-kinases/protein kinase B (PI3K/Akt) pathway-mediated autophagy in ovalbumin-induced airway inflammation in mice. Wild-type (WT) and TLR2-knockout (TLR2 −/− ) C57BL/6 mice were ovalbumin-sensitized and ovalbumin-challenged. In ovalbumin-challenged WT mice, enhanced expression of TLR2 in lung tissue, remarkable inflammatory cell infiltrates, goblet cell hyperplasia, and increased mucus production were observed. The number of inflammatory cells and interleukin-13 (IL-13) levels increased, while interferon-gamma (IFN-γ) levels decreased in bronchoalveolar lavage fluid. Expression of PI3K, phospho-Akt, Beclin-1 and LC3-II was enhanced significantly. These changes were mitigated dose-dependently in 3-methyl adenine-treated mice. In contrast, similar but weaker changes were found in ovalbumin-challenged TLR2 −/− mice, and the changes were not significantly attenuated by 3-methyl adenine treatment. These results indicate that TLR2 confers a pivotal role in allergic airway inflammation via regulating the PI3K/Akt signaling pathway-related autophagy in mice.

Tocilizumab has been reported to attenuate the “cytokine storm” in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI–7.19%–21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI–99.17% to–17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.

The DPC is a multiangle sensor that detects atmospheric parameters. However, the retrieval of high-precision and high-spatial-resolution aerosol products from the DPC remains a great challenge due to the ill-posed nature of the problem. Thus, a novel aerosol optical depth (AOD) retrieval algorithm was proposed using visible surface reflectance relationships (VISRRs). The VISRR algorithm accounts for the surface anisotropy and needs neither a shortwave infrared band nor a surface reflectance database that can retrieve AOD over dark and bright land cover. Firstly, moderate-resolution imaging spectroradiometer (MODIS) surface reflectance (MYD09) products were used to derive the preceding surface reflectance relationships (SRRs), which are related to surface types, scattering angle, and normalized difference vegetation index (NDVI). Furthermore, to solve the problem of the NDVI being susceptible to the atmosphere, an innovative method based on an iterative atmospheric correction was proposed to provide a realistic NDVI. The VISRR algorithm was then applied to the thirteen months of DPC multiangle data over the China region. AOD product comparison between the DPC and MODIS showed that they had similar spatial distribution, but the DPC had both high spatial resolution and coverage. The validation between the ground-based sites and the retrieval results showed that the DPC AOD performed best, with a Pearson correlation coefficient (R) of 0.88, a root mean square error (RMSE) of 0.17, and a good fraction (Gfrac) of 62.7%. Then, the uncertainties regarding the AOD products were discussed for future improvements. Our results revealed that the VISRR algorithm is an effective method for retrieving reliable, simultaneously high-spatial-resolution and full-surface-coverage AOD data with good accuracy.

China is planning to launch more and more optical remote-sensing satellites with high spatial resolution and multistep gains. Field calibration, the current operational method of satellite in-flight radiometric calibration, still does not have enough capacity to meet these demands. Gaofen-1 (GF-1), as the first satellite of the Chinese High-resolution Earth Observation System, has been specially arranged to obtain 22 images over clean ocean areas using the Wide Field Viewing camera. Following this, Rayleigh scattering calibration was carried out for the visible channels with these images after the appropriate data processing steps. To guarantee a high calibration precision, uncertainty was analyzed in advance taking into account ozone, aerosol optical depth (AOD), seawater salinity, chlorophyll concentration, wind speed and solar zenith angle. AOD and wind speed were found to be the biggest error sources, which were also closely coupled to the solar zenith angle. Therefore, the best sample data for Rayleigh scattering calibration were selected at the following solar zenith angle of 19–22° and wind speed of 5–13 m/s to reduce the reflection contributed by the water surface. The total Rayleigh scattering calibration uncertainties of visible bands are 2.44% (blue), 3.86% (green), and 4.63% (red) respectively. Compared with the recent field calibration results, the errors are −1.69% (blue), 1.83% (green), and −0.79% (red). Therefore, the Rayleigh scattering calibration can become an operational in-flight calibration method for the high spatial resolution satellites.

Glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) is a long-acting muscarinic antagonist/long-acting β -agonist fixed-dose combination therapy delivered by MDI, formulated using innovative co-suspension delivery technology. The PINNACLE-4 study evaluated the efficacy and safety of GFF MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) from Asia, Europe, and the USA. This article presents the results from the China subpopulation of PINNACLE-4. In this randomized, double-blind, placebo-controlled, parallel-group Phase III study (NCT02343458), patients received GFF MDI 18/9.6 µg, glycopyrrolate (GP) MDI 18 µg, formoterol fumarate (FF) MDI 9.6 µg, or placebo MDI (all twice daily) for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 second at Week 24. Secondary lung function endpoints and patient-reported outcome measures were also assessed. Safety was monitored throughout the study. Overall, 466 patients from China were included in the intent-to-treat population (mean age 63.6 years, 95.7% male). Treatment with GFF MDI improved the primary endpoint compared to GP MDI, FF MDI, and placebo MDI (least squares mean differences: 98, 104, and 173 mL, respectively; all 0.0001). GFF MDI also improved daily total symptom scores and time to first clinically important deterioration versus monocomponents and placebo MDI, and Transition Dyspnea Index focal score versus placebo MDI. Rates of treatment-emergent adverse events were similar across the active treatment groups and slightly higher in the placebo MDI group. GFF MDI improved lung function and daily symptoms versus monocomponents and placebo MDI and improved dyspnea versus placebo MDI. All treatments were well tolerated with no unexpected safety findings. Efficacy and safety results were generally consistent with the global PINNACLE-4 population, supporting the use of GFF MDI in patients with COPD from China.

Background Patients with chronic obstructive pulmonary disease (COPD) often have coagulation abnormalities. However, the factors that lead to coagulation dysfunction in acute exacerbation of COPD (AECOPD) remain insufficiently explored. This study aimed to investigate the factors affecting coagulation status in patients with COPD and their influence on thrombosis. Methods Data of COPD patients, including 135 cases in acute exacerbation stage and 44 cases in stable stage from Nov 2016 to Nov 2019 in our hospital, were collected. Healthy people (n = 135) were enrolled as the controls. The coagulation parameters, blood gas indexes and blood routine examination results were collected and analyzed. Results White blood count (WBC), neutrophil count, neutrophil percentage (N%), platelet (PLT), prothrombin time (PT), international normalized ratio (INR), fibrinogen (FIB), and activated partial thromboplastin time (APTT) increased, plasma thrombin time (TT) decreased in AECOPD group compared with the control group. In AECOPD group, PT, APTT, and FIB were positively correlated with neutrophils and C‐reaction protein levels. PT was positively correlated with PCO2 and negatively with pH. Thrombosis was observed in five acute exacerbation and three stable stage COPD patients. Conclusions Patients with AECOPD presented abnormal coagulation status, which was correlated to infection and hypercapnia and might be potentially the risk factor of thrombosis. Patients with AECOPD often have coagulation abnormalities. In this study, some factors such as infection and hypercapnia were found to be related to the coagulation abnormality and thrombosis in those patients

SummarySmall cell lung cancer (SCLC) is a highly lethal malignancy with the 5-year survival rate of less than 7%. Chemotherapy-resistance is a major challenge for SCLC treatment in clinic. In the study, we developed a high-throughput drug screen strategy to identify new drugs that can enhance the sensitivity of chemo-drug cisplatin in SCLC. This screen identified auranofin, a US Food and Drug Administration (FDA)-approved drug used therapeutically for rheumatoid arthritis, as a sensitizer of cisplatin. Further study validated that auranofin synergistically enhanced the anti-tumor activity of cisplatin in chemo-resistant SCLC cells, which was accompanied by the enhanced induction of cell cycle arrest and apoptosis. The synergistic action of auranofin and cisplatin was through ROS overproduction, thereby leading to mitochondrial dysfunction and DNA damage. Furthermore, in vivo study demonstrated that the combination treatment of auranofin and cisplatin dramatically inhibited tumor growth in SCLC. Therefore, our study provides a rational basis for further clinical study to test whether auranofin could enhance the sensitivity of cisplatin-based therapy in SCLC patients.

Background: Glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) is a long-acting muscarinic antagonist/long-acting [[beta].sub.2]-agonist fixed-dose combination therapy delivered by MDI, formulated using innovative co-suspension delivery technology. The PINNACLE-4 study evaluated the efficacy and safety of GFF MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) from Asia, Europe, and the USA. This article presents the results from the China subpopulation of PINNACLE-4. Methods: In this randomized, double-blind, placebo-controlled, parallel-group Phase III study (NCT02343458), patients received GFF MDI 18/9.6 [micro]g, glycopyrrolate (GP) MDI 18 [micro]g, formoterol fumarate (FF) MDI 9.6 [micro]g, or placebo MDI (all twice daily) for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 second at Week 24. Secondary lung function endpoints and patient-reported outcome measures were also assessed. Safety was monitored throughout the study. Results: Overall, 466 patients from China were included in the intent-to-treat population (mean age 63.6 years, 95.7% male). Treatment with GFF MDI improved the primary endpoint compared to GP MDI, FF MDI, and placebo MDI (least squares mean differences: 98, 104, and 173 mL, respectively; all P[less than or equal to]0.0001). GFF MDI also improved daily total symptom scores and time to first clinically important deterioration versus monocomponents and placebo MDI, and Transition Dyspnea Index focal score versus placebo MDI. Rates of treatment-emergent adverse events were similar across the active treatment groups and slightly higher in the placebo MDI group. Conclusion: GFF MDI improved lung function and daily symptoms versus monocomponents and placebo MDI and improved dyspnea versus placebo MDI. All treatments were well tolerated with no unexpected safety findings. Efficacy and safety results were generally consistent with the global PINNACLE-4 population, supporting the use of GFF MDI in patients with COPD from China. Keywords: bronchodilator, COPD, co-suspension delivery technology, LAMA/LABA, exacerbations