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In ORIENT-11, first-line sintilimab + pemetrexed-platinum significantly improved PFS compared with placebo + pemetrexed-platinum in patients with advanced metastatic nonsquamous non-small-cell lung cancer (AMnsqNSCLC). The study met the primary endpoint of PFS as of 15November2019. Here we report final survival analysis from ORIENT-11 (NCT03607539) using a 15September2021 data cutoff.Patients with treatment-naïve locally AMnsqNSCLC without sensitizing EGFR or ALK genomic tumor aberrations were randomly assigned to sintilimab + pemetrexed-platinum (n = 266) or placebo + pemetrexed-platinum (n = 131). Patients were stratified by PD-L1 expression, platinum-chemotherapy, and gender. Treatment continued until PD, unacceptable toxicity, or a maximum of 24 months. Patients in the placebo + pemetrexed-platinum arm could be sequenced to second-line sintilimab monotherapy, contingent upon PD. Response was assessed (RECISTv.1.1) by blinded independent radiographic review committee. Primary endpoint was PFS. OS was a secondary endpoint and defined from date of randomization to date of death due to any cause. Final OS analysis was defined as approximately 2 years after last patient randomized or when approximately 65 % of patients died, whichever first.At data cutoff of final OS analysis, median study follow-up was 30.8 months. Of 397 patients, 243 OS events were observed (sintilimab + pemetrexed-platinum:151[57 %];placebo + pemetrexed-platinum:92 [70 %]). Of the patients in placebo + pemetrexed-platinum arm, 47 % crossed over to sintilimab monotherapy per protocol. Median OS was 24.2 months in sintilimab + pemetrexed-platinum arm and 16.8 months in placebo + pemetrexed-platinum arm (HR:0.65[95 % CI:0.50,0.85]). Estimated 2-year OS rates were 50 %(sintilimab + pemetrexed-platinum) and 32 %(placebo + pemetrexed-platinum). After adjusting for the crossover effect, OS treatment effect was more pronounced with HR 0.52 (95 % CI:0.38,0.69). OS benefit across all prespecified subgroups was largely consistent with that observed in the ITT population.In the ORIENT-11 final OS analysis, sintilimab + pemetrexed-platinum demonstrated improved OS compared to placebo + pemetrexed-platinum when administered as first-line therapy in AMnsqNSCLC without EGFR or ALK genomic tumor aberrations.

Background: The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has gradually become a global public health crisis. Some patients who have recovered from COVID-19 subsequently tested positive again for SARS-CoV-2 after discharge (retesting-positive, RTP). However, the underlying mechanism is unknown. Methods: Here, 30 RTP patients, 20 convalescent patients, and 20 healthy controls were enrolled for analysis of the immunological characteristics of their peripheral blood mononuclear cells (PBMCs). Furthermore, we sought to comprehensively characterize the transcriptional changes in the three groups by transcriptome sequencing. Findings: It was found that the absolute numbers of CD4+ T cells, CD8+ T cells, and NK cells were not decreased remarkably, while the expression of activation markers on these cells was significantly decreased in RTP patients. Furthermore, the percentage of granzyme B-producing T cells was also decreased in RTP patients compared with that in convalescent patients. Moreover, the high expression of inhibitor of differentiation-1 (ID1) and the low expression of IFITM10 may be associated with the insufficient activation of immune cells and RTP occurrence. Interpretation: Our findings provide insights into the impaired immune function and pathogenesis of RTP occurrence in COVID-19, which may contribute to the development of immunotherapy for RTP patients. Funding Statement: This work was supported by China National Center for Biotechnology Development (2020YFC0843800 and 2020YFC0846800), Ministry of Science and Technology of China (2020TFC0844100), and China Postdoctoral Science Foundation (2020T130112ZX). Declaration of Interests: The authors declare no potential conflict of interest. Ethics Approval Statement: The studies were approved by the Ethics Committee of the First Affiliated Hospital of the University of Science & Technology of China (2020-XG(H)-005) and Peking University First Hospital (2020-Research-112) for Emerging Infectious Diseases. Experiments were conducted in accordance with the ethical guidelines of the 1975 Declaration of Helsinki, the Principles of Good Clinical Practice, and the guidelines of China’s regulatory requirements.

PurposesTo evaluate the diagnostic efficiency of metagenomics next generation sequencing (mNGS) assay in severe leptospirosis and its role on prognosis. Methods We retrospectively reviewed the medical records of patients with confirmed leptospirosis from Jan. 1, 2019 to Dec. 31, 2021 from three hospitals. Detailed data including socio-demographic data, clinical manifestations, laboratory examination results, CT images etc. were collected and analyzed. Results Six severe cases were included in this study. All were diagnosed by positive mNGS results. Three of the patients were also polymerase chain reaction examined and presented negative results. Five patients were diagnosed by mNGS assay within two or three days and antibiotics were down-graded to ceftriaxone in them. All of them were cured finally. One case, who was diagnosed by mNGS late on day 5, died. Conclusions mNGS is highly efficient in diagnosing leptospirosis and could possibly reduce the mortality rate if used at an early stage.

Safely interacting with other traffic participants is one of the core requirements for autonomous driving, especially in intersections and occlusions. Most existing approaches are designed for particular scenarios and require significant human labor in parameter tuning to be applied to different situations. To solve this problem, we first propose a learning-based Interaction Point Model (IPM), which describes the interaction between agents with the protection time and interaction priority in a unified manner. We further integrate the proposed IPM into a novel planning framework, demonstrating its effectiveness and robustness through comprehensive simulations in highly dynamic environments., 8 pages, 17 figures, RA-L accepted, september, 2022, preprint version

To verify the diagnostic utility of recombinant fusion protein ESAT6-CPF10 (EC), a novel skin test reagent to detect Mycobacterium tuberculosis infection.A multi-centered, double-blind, randomized controlled trial was conducted from December 17, 2015, to March 2, 2018. Participants involved in this study included those with active tuberculosis (TB), suspected pulmonary TB, or non-TB pulmonary disease. Each participant received three tests simultaneously, TB-specific enzyme-linked immunospot assay (T-SPOT.TB), tuberculin skin test (TST), and EC skin test (ECST), and adverse events were reported.Diagnostic accuracy was analyzed using data from 1085 protocol-compliant participants. The sensitivities of the ECST, TST, and T-SPOT.TB were 91.2% (95% CI, 89.0-93.2%), 91.4% (95% CI, 89.1-93.3%), and 92.1% (95% CI, 89.9-93.9%), respectively. The specificities of the ECST (69.7%, 95% CI, 64.5-74.5%) and T-SPOT.TB (76.1%, 95% CI, 71.2-80.5%) were significantly higher than the TST (54.4%, 95% CI, 48.9-59.7%). The agreements between ECST and TST (kappa = 0.632) and between ECST and T-SPOT.TB (kappa = 0.780) were substantial. No severe adverse event was reported.The diagnostic performance of the ECST was close to the T-SPOT.TB assay in the detection of TB infection and indicated good potential for clinical application in common scenarios.

Low-Cost Sensors (LCS) of fine particulate matter (PM2.5) have been widely used to supplement regular air quality monitoring stations. However, the sensor output is impacted by environmental factors, especially relative humidity, and must be calibrated to yield estimates of concentrations. In this study, we evaluate the performance of a linear model and a generalized additive model (GAM) to calibrate the output of LCS PM2.5 measurements in terms of different relative humidity levels. The method is based on co-located measurements from an LCS and a conventional reference monitor at two sites in an urban area in northern China. A stepwise variable selection of air pollutant concentrations and meteorological observations is used to select inputs to the model in order to improve the calibration ability. The results show that when relative humidity is below 75%, linear calibration of LCS PM2.5 observations can output PM2.5 mass concentrations close to the reference method with a correlation coefficient (R2) of 0.86. When relative humidity is above 75%, the GAM calibration model significantly outperforms the linear model, with an R2 of approximately 0.83. Overall, the linear model exhibits good fitness in dry conditions, while the GAM captures PM2.5 variations best in humid conditions. We conclude that low-cost PM2.5 sensors are sensitive to relative humidity and that therefore condition-specific calibration methods need to be used to improve the quality of the data as well as to improve the match with reference measurements. Copyright © 2021 American Association for Aerosol Research

Rongchang Chen,1 Nanshan Zhong,2 Hao-Yan Wang,3 Li Zhao,4 Xiaodong Mei,5 Zhiqiang Qin,6 Juan Huang,7 Pryseley N Assam,8 Andrea Maes,9 Shahid Siddiqui,10 Ubaldo J Martin,10 Colin Reisner9 1Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Diseases, National Clinical Research Centre for Respiratory Diseases, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Sheng Jing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 5Anhui Provincial Hospital, Hefei, Anhui, People’s Republic of China; 6The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City, Guangxi Zhuang Autonomous Region, People’s Republic of China; 7Formerly of AstraZeneca, Shanghai, People’s Republic of China; 8AstraZeneca, Shanghai, People’s Republic of China; 9AstraZeneca, Morristown, NJ, USA; 10AstraZeneca, Gaithersburg, MD, USACorrespondence: Nanshan ZhongGuangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Diseases, National Clinical Research Centre for Respiratory Diseases, First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou 510120, Guangdong, People’s Republic of ChinaTel +86 20 83062719Email nanshan@vip.163.comBackground: Glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) is a long-acting muscarinic antagonist/long-acting β2-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 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.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≤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

BACKGROUND: Bevacizumab is a monoclonal antibody (mAb) against vascular endothelial growth factor (VEGF) and used for treatments of various cancers. Due to the high costs of bevacizumab treatments, a biosimilar provides an affordable alternative therapy for cancer patients. METHODS: In this randomized, double-blind, multicenter, phase 3 study, locally advanced, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC) patients with wild-type epidermal growth factor receptor were enrolled and randomized (1:1) into IBI305 or bevacizumab groups. Patients received 6 cycles of paclitaxel/carboplatin plus IBI305 or bevacizumab 15 mg/kg intravenously followed by IBI305 or bevacizumab 7.5 mg/kg maintenance until disease progression, unacceptable toxicity or death. The primary endpoint was confirmed objective response rate (ORR) by an independent radiological review committee (IRRC) and secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS) and safety. RESULTS: A total of 450 NSCLC patients were enrolled (224 in IBI305 group and 226 in bevacizumab group). ORRs were 44.3% for IBI305 and 46.4% for bevacizumab, and the ORR ratio was 0.95 (90% CI: 0.803 to 1.135), within the predefined equivalence margin of 0.75 to 1.33. No significant difference in PFS (7.64 vs. 7.77 m, P=0.9987) was observed between the 2 groups. Serious adverse events (AEs) occurred in 33.5% (75/224) of patients in the IBI305 group and 37.6% (85/226) in the bevacizumab group. AEs ≥ grade 3 were similar in the IBI305 and bevacizumab groups [84.4% (189/224) vs. 89.8% (203/226), P=0.085]. CONCLUSIONS: IBI305 is similar to bevacizumab in terms of efficacy and safety. TRIAL REGISTRATION: Clinicaltrials.org Identifier: NCT02954172. Registered on 3 November 2016. Https://clinicaltrials.gov/.

The aim of this study was to investigate the efficacy and safety of tratinterol hydrochloride in bronchial asthma (BA) treatment.Patients enrolled in this study were distributed randomly into a treatment group (tratinterol hydrochloride) and an active control group (procaterol hydrochloride) and were treated for 2 weeks after running-in. The end points were changes in pulmonary function and clinical symptoms after administration. Safety indices were physical examinations, laboratory testing and spontaneous reporting.We enrolled 732 subjects, -365 in the treatment group and 367 in the active control group. Forced expiratory volume (FEVTratinterol hydrochloride was effective, safe and not inferior to procaterol hydrochloride in treating BA.

Small 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.

e21157 Background: In ORIENT-11, first-line (1L) SPP improved progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and duration of response (DoR) compared with placebo plus pemetrexed-platinum (PPP) in pts with AMnsqNSCLC. We report outcomes from ORIENT-11 (NCT03607539) for pts treated with SPP with stage III (b & c) compared with stage IV disease. Methods: Pts with treatment-naïve locally AMnsqNSCLC without sensitizing EGFR/ALK alterations were randomly assigned to SPP (n = 266) or PPP (n = 131), stratified by PD-L1 expression, platinum-chemotherapy and sex. Primary endpoint was PFS (RECIST v1.1). Secondary endpoints included OS, ORR, DoR and safety. Kaplan-Meier method was used to analyze median PFS, OS and DoR. Stratified Cox model was used to analyze the hazard ratio (HR) of SPP vs. PPP. Clopper-Pearson method was used to calculate the 95% confidence intervals (CI) of ORR for each group. Miettinen-Nurminen method was used to analyze 95% CI of ORR difference between SPP and PPP. Data cutoff for OS data was September 15, 2021, providing a median follow-up of 30.8 months. Cutoff for other data was November 15, 2019, providing a median follow-up of 8.9 months. Results: 21 pts (7.9%) receiving SPP had stage III disease and 245 pts (92.1%) had stage IV disease. Baseline sex, age and PD-L1 expression ≥1% were similar between subgroups (Table). There were differences between subgroups in number of pts receiving carboplatin and ECOG performance status at baseline. PFS, OS, ORR and DoR outcomes were comparable between pts with stage III and stage IV disease based on the ad-hoc analyses. Any-grade adverse events (AEs) (100.0% vs. 99.6%) and AEs of Grade ≥3 (57.1% vs. 62.0%) were similar in pts with stage III and stage IV disease. Conclusions: In ORIENT-11, outcomes for pts receiving SPP as 1L therapy in AMnsqNSCLC with stage III and stage IV disease were comparable. Clinical trial information: NCT03607539. [Table: see text]

Sintilimab plus chemotherapy significantly prolonged progression-free survival (PFS) compared with chemotherapy alone in nonsquamous NSCLC in the ORIENT-11 study. Updated overall survival (OS) and PFS data and corresponding biomarker analyses are reported here.In this study, a total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC were assigned to sintilimab plus chemotherapy combination treatment (combo) group or placebo plus chemotherapy treatment group. The patients were stratified by programmed death-ligand 1 (PD-L1) expression levels. Immune signature profiles from tumor RNA sequencing and PD-L1 immunohistochemistry were correlated with clinical outcome to identify predictive biomarkers.As of January 2021, with median follow-up of 22.9 months, median OS was significantly improved in the combo group compared with the placebo plus chemotherapy treatment group (not reached versus 16.8 mo; hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.45-0.79, p = 0.0003). High or medium immune cell infiltration was strongly associated with improved PFS in the combo group, in contrast to absent or low immune cell infiltration, which suggests that chemotherapy could not prime "immune deserts" to obtain benefit from programmed cell death protein-1 inhibition. In particular, high major histocompatibility complex (MHC) class II presentation pathway expression was significantly correlated with prolonged PFS (HR = 0.32, 95% CI: 0.19-0.54, p0.0001) and OS (HR = 0.36, 95% CI: 0.20-0.64, p = 0.0005) in the combo group. Importantly, patients with low or absent PD-L1 but high MHC class II expression could still benefit from the combo treatment. In contrast, MHC class I antigen presentation pathway was less relevant in this combination setting.The addition of sintilimab to chemotherapy resulted to significantly longer OS in nonsquamous NSCLC. Expression of MHC class II antigen presentation pathway could identify patients benefiting most from this combination.

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

During winter 2018, the 16 prefecture-level cities in Anhui Province, Western Yangtze River Delta region, China had very high PM

As a result of the lockdown (LD) control measures enacted to curtail the COVID-19 pandemic in Wuhan, almost all non-essential human activities were halted beginning on January 23, 2020 when the total lockdown was implemented. In this study, changes in the concentrations of the six criteria air pollutants (PM2.5, PM10, SO2, NO2, CO, and O3) in Wuhan were investigated before (January 1 to 23, 2020), during (January 24 to April 5, 2020), and after the COVID-19 lockdown (April 6 to June 20, 2020) periods. Also, the relationships between the air pollutants and meteorological variables during the three periods were investigated. The results showed that there was significant improvement in air quality during the lockdown. Compared to the pre-lockdown period, the concentrations of NO2, PM2.5, PM10, and CO decreased by 50.6, 41.2, 33.1, and 16.6%, respectively, while O3 increased by 149% during the lockdown. After the lockdown, the concentrations of PM2.5, CO and SO2 declined by an additional 19.6, 15.6, and 2.1%, respectively. However, NO2, O3, and PM10 increased by 55.5, 25.3, and 5.9%, respectively, compared to the lockdown period. Except for CO and SO2, WS had negative correlations with the other pollutants during the three periods. RH was inversely related with all pollutants. Positive correlations were observed between temperature and the pollutants during the lockdown. Easterly winds were associated with peak PM2.5 concentrations prior to the lockdown. The highest PM2.5 concentrations were associated with southwesterly wind during the lockdown, and northwesterly winds coincided with the peak PM2.5 concentrations after the lockdown. Although, COVID-19 pandemic had numerous negative effects on human health and the global economy, the reductions in air pollution and significant improvement in ambient air quality likely had substantial short-term health benefits. This study improves the understanding of the mechanisms that lead to air pollution under diverse meteorological conditions and suggest effective ways of reducing air pollution in Wuhan., Graphical abstract Unlabelled Image, Highlights • NO2 reduced by half during COVID-19 lockdown compared to the pre-lockdown. • PM2.5 and PM10 decreased substantially during lockdown. • O3 increased by 149% during lockdown form lower NOx and higher solar radiation. • Meteorology has significant impacts in the air pollution concentrations. • Local sources dominated the air pollutant emissions in Wuhan.

Unprecedented travel restrictions due to the COVID-19 pandemic caused remarkable reductions in anthropogenic emissions, however, the Beijing area still experienced extreme haze pollution even under the strict COVID-19 controls. Generalized Additive Models (GAM) were developed with respect to inter-annual variations, seasonal cycles, holiday effects, diurnal profile, and the non-linear influences of meteorological factors to quantitatively differentiate the lockdown effects and meteorology impacts on concentrations of nitrogen dioxide (NO2) and fine particulate matters (PM2.5) at 34 sites in the Beijing area. The results revealed that lockdown measures caused large reductions while meteorology offset a large fraction of the decrease in surface concentrations. GAM estimates showed that in February, the control measures led to average NO2 reductions of 19 μg/m3 and average PM2.5 reductions of 12 μg/m3. At the same time, meteorology was estimated to contribute about 12 μg/m3 increase in NO2, thereby offsetting most of the reductions as well as an increase of 30 μg/m3 in PM2.5, thereby resulting in concentrations higher than the average PM2.5 concentrations during the lockdown. At the beginning of the lockdown period, the boundary layer height was the dominant factor contributing to a 17% increase in NO2 while humid condition was the dominant factor for PM2.5 concentrations leading to an increase of 65% relative to the baseline level. Estimated NO2 emissions declined by 42% at the start of the lockdown, after which the emissions gradually increased with the increase of traffic volumes. The diurnal patterns from the models showed that the peak of vehicular traffic occurred from about 12pm to 5pm daily during the strictest control periods. This study provides insights for quantifying the changes in air quality due to the lockdowns by accounting for meteorological variability and providing a reference in evaluating the effectiveness of control measures, thereby contributing to air quality mitigation policies., Graphical abstract Image 1

Lockdown measures to curtail the COVID-19 pandemic in China halted most non-essential activities on January 23, 2020. Despite significant reductions in anthropogenic emissions, the Beijing-Tianjin-Hebei (BTH) region still experienced high air pollution concentrations. Employing two emissions reduction scenarios, the Community Multiscale Air Quality (CMAQ) model was used to investigate the PM

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. Electronic Supplementary Material Supplementary material is available in the online version of this article at 10.1007/s11684-020-0824-3 and is accessible for authorized users.

The holiday effect is a useful tool to estimate the impact on air pollution due to changes in human activities. In this study, we assessed the variations in concentrations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) during the holidays in the heating season from 2014 to 2018 based on daily surface air quality monitoring measurements in Beijing. A Generalized Additive Model (GAM) is used to analyze pollutant concentrations for 34 sites by comprehensively accounting for annual, monthly, and weekly cycles as well as the nonlinear impacts of meteorological factors. A Saturday effect was found in the downtown area, with about 4% decrease in PM2.5 and 3% decrease in NO2 relative to weekdays. On Sundays, the PM2.5 concentrations increased by about 5% whereas there were no clear changes for NO2. In contrast to the small effect of the weekend, there was a strong holiday effect throughout the region with average increases of about 22% in PM2.5 and average reductions of about 11% in NO2 concentrations. There was a clear geographical pattern in the strength of the holiday effect. In rural areas the increase in PM2.5 is related to the proportion of coal and biomass consumption for household heating. In the suburban areas between the Fifth Ring Road and Sixth Ring Road there were larger reductions in NO2 than downtown which might be due to decreased traffic as many people return to their hometown for the holidays. This study provides insights into the pattern of changes in air pollution due to human activities. By quantifying the changes, it also provides insights for improvements in air quality due to control policies implemented in Beijing during the heating season., Graphical abstract Unlabelled Image, Highlights • During the holidays, PM2.5 is about 22% higher and NO2 is about 11% lower in the greater Beijing area. • On Saturdays, PM2.5 is about 4% lower and NO2 is about 3% lower in downtown Beijing. • On Sundays, PM2.5 is about 5% higher but NO2 is similar to weekdays. • Holiday increases in PM2.5 are about 18.4% larger in the southwest and northeast than in other rural areas. • Suburban areas have larger holiday reductions in NO2 than downtown areas.

Sintilimab, an anti-programmed death 1 antibody, plus pemetrexed and platinum had revealed promising efficacy for nonsquamous NSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to compare the efficacy and safety of sintilimab with placebo, both in combination with such chemotherapy (ClinicalTrials.gov: NCT03607539).A total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC without sensitizing EGFR or anaplastic lymphoma kinase genomic aberration were randomized (2:1 ratio) to receive either sintilimab 200 mg or placebo plus pemetrexed and platinum once every 3 weeks for four cycles, followed by sintilimab or placebo plus pemetrexed therapy. Crossover or treatment beyond disease progression was allowed. The primary end point was progression-free survival (PFS) as judged by an independent radiographic review committee.As of November 15, 2019, the median follow-up was 8.9 months. The median PFS was significantly longer in the sintilimab-combination group than that in the placebo-combination group (8.9 versus 5.0 mo; hazard ratio, 0.482, 95% confidence interval [CI]: 0.362-0.643; p0.00001). The confirmed objective response rate was 51.9% (95% CI: 45.7%-58.0%) in the sintilimab-combination group and 29.8% (95% CI: 22.1%-38.4%) in placebo-combination group. The incidence of grade 3 or higher adverse events was 61.7% in sintilimab-combination group and 58.8% in placebo-combination group.In Chinese patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC, the addition of sintilimab to chemotherapy with pemetrexed and platinum resulted in considerably longer PFS than with chemotherapy alone with manageable safety profiles.

Drifting is a complicated task for autonomous vehicle control. Most traditional methods in this area are based on motion equations derived by the understanding of vehicle dynamics, which is difficult to be modeled precisely. We propose a robust drift controller without explicit motion equations, which is based on the latest model-free deep reinforcement learning algorithm soft actor-critic. The drift control problem is formulated as a trajectory following task, where the error-based state and reward are designed. After being trained on tracks with different levels of difficulty, our controller is capable of making the vehicle drift through various sharp corners quickly and stably in the unseen map. The proposed controller is further shown to have excellent generalization ability, which can directly handle unseen vehicle types with different physical properties, such as mass, tire friction, etc.

Background: Tocilizumab is reported to be able to attenuate the "cytokine storm" in COVID-19 patients. We tried to ascertain the effectiveness and safety of tocilizumab in COVID-19 and identify patients most likely to be benefit from the treatment. Methods: This was a randomized, controlled, open-label, multicenter trial at 6 hospitals in Anhui and Hubei. Patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care, or standard care alone. The first dose of tocilizumab was 400 mg, diluted in 100 ml 0.9% saline, and intravenous dripped in more than 1 h. A second dose was given if a patient remained febrile for 24 hours after the first dose. The primary endpoint was the cure rate. Primary analysis was done in the intention -to -treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. Findings: Between Feb 13, 2020, and March 13, 2020, 65 patients were enrolled and randomly assigned to a treatment group (33 to tocilizumab and 32 to the controls). One patient in the control group, who aggravated severely 3 days after randomization, was transferred to the tocilizumab group. The cure rate in tocilizumab group was higher than that in the controls but not significant (94.12% vs 87.10%, P=0.4133). Adverse events were recorded in 20 (58.82%) of 34 tocilizumab recipients versus 4 (12.90%) of 31 in the controls. No serious adverse events were reported in tocilizumab group. Interpretation: Tocilizumab treatment did not increase the cure rate of COVID-19. A large scale of study enrolling more patients is needed. However，tocilizumab can improve oxygenation without significant influence on the time virus load tunes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab should be recommended for better disease management. Trial Registration: This trial was registered in Chinese Clinical Trial Registry (Number: ChiCTR2000029765). Funding: This work was supported by Department of Science and Technology of Anhui Province and Health Commission of Anhui Province (grant number: 202004a07020001) and the China National Center for Biotechnology Development (grant number: 2020YFC0843800). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study protocol was approved by the Medical Research Ethics Committee of Anhui Provincial Hospital, the First Affiliated Hospital of USTC [approval no. 2020-XG (H)-015]. The authors committed to protect the patient’s privacy and comply with the Helsinki Declaration.

During winter 2018, the 16 prefecture-level cities in Anhui Province, Western Yangtze River Delta region, China had very high PM2.5 concentrations and prolonged pollution days. The impact of regional transport in the formation, accumulation, as well as dispersion of fine particulate matter (PM2.5) in Anhui Province was very significant. This study quantified and analyzed the vertical transport of PM2.5 in three major cities (Hefei, Fuyang, and Suzhou) of Anhui Province in January and July 2018 using the Weather Research and Forecasting (WRF) model coupled with the Community Multiscale Air Quality (CMAQ) model. The results of the inter-regional transport of PM2.5 revealed the dominant transport pathways for the three cities. The flux mainly flowed into Fuyang from Henan (2.23 and 1.42 kt/day in January and July, respectively) and Bozhou (1.96 and 1.21 kt/day in January and July, respectively), while the main flux from Fuyang flowed into Henan (−2.15 kt/day) and Lu'an (−1.91 kt/day) in January and Henan (−0.34 kt/day) and Bozhou (−0.29 kt/day) in July. In addition, the dominant transport pathways and the heights at which they occurred were identified: the northwest-southeast and northeast-south pathways in both winter and summer at both lower (˂300 m) and higher (≥300 m) levels for Fuyang; the northwest-south and northeast-southwest pathways in winter (at both lower and upper levels) and northwest-east and northeast-southwest pathways in summer at lower and upper levels for Hefei; and the northwest-southeast and northeast-south pathways in both winter (from 50 m up to the top level) and summer (between 100 and 300 m) for Suzhou. Furthermore, the intensities of daily PM2.5 transport fluxes in Fuyang during the atmospheric pollution episode (APE1) were stronger than the monthly average. These results show that joint emission controls across multiple cities along the identified pathways are urgently needed to reduce winter episodes.

Unprecedented travel restrictions due to the COVID-19 pandemic caused remarkable reductions in anthropogenic emissions, however, the Beijing area still experienced extreme haze pollution even under the strict COVID-19 controls. Generalized Additive Models (GAM) were developed with respect to inter-annual variations, seasonal cycles, holiday effects, diurnal profile, and the non-linear influences of meteorological factors to quantitatively differentiate the lockdown effects and meteorology impacts on concentrations of nitrogen dioxide (NO2) and fine particulate matters (PM2.5) at 34 sites in the Beijing area. The results revealed that lockdown measures caused large reductions while meteorology offset a large fraction of the decrease in surface concentrations. GAM estimates showed that in February, the control measures led to average NO2 reductions of 19 µg/m3 and average PM2.5 reductions of 12 µg/m3. At the same time, meteorology was estimated to contribute about 12 µg/m3 increase in NO2, thereby offsetting most of the reductions as well as an increase of 30 µg/m3 in PM2.5, thereby resulting in concentrations higher than the average PM2.5 concentrations during the lockdown. At the beginning of the lockdown period, the boundary layer height was the dominant factor contributing to a 17% increase in NO2 while humid condition was the dominant factor for PM2.5 concentrations leading to an increase of 65% relative to the baseline level. Estimated NO2 emissions declined by 42% at the start of the lockdown, after which the emissions gradually increased with the increase of traffic volumes. The diurnal patterns from the models showed that the peak of vehicular traffic occurred from about 12pm to 5pm daily during the strictest control periods. This study provides insights for quantifying the changes in air quality due to the lockdowns by accounting for meteorological variability and providing a reference in evaluating the effectiveness of control measures, thereby contributing to air quality mitigation policies.

Lockdown measures to curtail the COVID-19 pandemic in China halted most non-essential activities on January 23, 2020. Despite significant reductions in anthropogenic emissions, the Beijing-Tianjin-Hebei (BTH) region still experienced high air pollution concentrations. Employing two emissions reduction scenarios, the Community Multiscale Air Quality (CMAQ) model was used to investigate the PM2.5 concentrations change in this region. The model using the scenario (C3) with greater traffic reductions performed better compared to the observed PM2.5. Compared with the no reductions base-case (scenario C1), PM2.5 reductions with scenario C3 were 2.70, 2.53, 2.90, 2.98, 3.30, 2.81, 2.82, 2.98, 2.68, and 2.83 μg/m3 in Beijing, Tianjin, Shijiazhuang, Baoding, Cangzhou, Chengde, Handan, Hengshui, Tangshan, and Xingtai, respectively. During high-pollution days in scenario C3, the percentage reductions in PM2.5 concentrations in Beijing, Tianjin, Shijiazhuang, Baoding, Cangzhou, Chengde, Handan, Hengshui, Tangshan, and Xingtai were 3.76, 3.54, 3.28, 3.22, 3.57, 3.56, 3.47, 6.10, 3.61, and 3.67%, respectively. However, significant increases caused by unfavorable meteorological conditions counteracted the emissions reduction effects resulting in high air pollution in BTH region during the lockdown period. This study shows that effective air pollution control strategies incorporating these results are urgently required in BTH to avoid severe pollution.

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.

BACKGROUND Family with sequence similarity 83 member A (FAM83A) can promote tumor cell proliferation and facilitate epidermal growth factor tyrosine kinase inhibitor resistance in some malignant tumors, but its role in lung cancer has not been directly explored. OBJECTIVE We investigated FAM83A expression in lung adenocarcinoma (LUAD) and its significance in clinicopathologic characteristics and prognosis of the disease. PATIENTS AND METHODS We analyzed the mRNA expression of FAM83A in LUAD and normal (or adjacent) lung tissues from Oncomine database firstly. Then, we detected FAM83A protein expression in five paired fresh LUAD and adjacent lung tissue specimens from patients in our hospital by Western blotting. In addtion, FAM83A expression in 86 paraffin-embedded archived LUAD samples was evaluated by Immunohistochemistry, and the correlations between FAM83A expression and clinicopathologic characteristics and prognosis of the patients were analyzed. RESULTS Oncomine data analysis manifested that FAM83A mRNA expression was increased in LUAD. Western blotting revealed higher FAM83A expression in fresh LUAD tissues than in the adjacent lung tissues (P= 0.036). Immunohistochemistry analysis on 86 paraffin samples further demonstrated that the LUAD tissue had higher FAM83A expression than adjacent lung tissue (P< 0.001). The correlation analysis revealed that advanced stage tumors (stage III-IV) had higher FAM83A expression than early stage tumors (stage I-II) (P= 0.004). High FAM83A expression was significantly associated with lymphnode involvement and clinical staging (P= 0.008 and 0.008 respectively). Univariate and multivariate Cox regression analysis manifested that FAM83A expression was an independent predictive factor for poor survival. Kaplan-Meier survival curves showed that patients with higher FAM83A expression had shorter overall survival than those with lower FAM83A expressions (P= 0.002). CONCLUSION FAM83A is upregulated in advanced LUAD and is related to unfavorible prognosis. FAM83A might be a novel diagnostic and prognositic biomarker for LUAD.

Small 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.

e21072 Background: Penpulimab is a human IgG1 monoclonal antibody (mAb) directed against human programmed cell death-1 (PD-1). Penpulimab, with its unique binding epitope, was engineered to eliminate Fc-mediated effector function that compromises anti-tumor immune cell function, and to optimize receptor occupancy by improving duration of drug binding. As a promising multi-target tyrosine kinase inhibitor (TKI), anlotinib significantly improved overall survival in advanced NSCLC patients (pts) in the phase 3 trial ALTER0303. Antiangiogenesis therapy combined with PD-1/PD-L1 inhibitors has shown excellent efficacy in advanced NSCLC pts. This is the trial evaluating chemo-free combination of penpulimab plus anlotinib in treatment-naive advanced NSCLC pts regardless of PD-L1 expression (NCT03866980). Methods: Pts with previously untreated, stage IIIB/IIIC/IV non-squamous NSCLC without sensitizing mutation of the epidermal growth factor receptor (EGFR) gene or translocation of the anaplastic lymphoma kinase (ALK) gene were enrolled. Eligible pts received penpulimab 200mg Q3W in combination with anlotinib 12mg QD (2 weeks on 1 week off) until loss of clinical benefit or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included ORR, disease control rate (DCR), duration of response (DoR) and overall survival. Results: As of January 13, 2021, 26 pts had received the combination therapy of penpulimab plus anlotinib (median age 59.5yrs [range 30-71], 76.9% male, 76.9% ECOG PS 1), with a median treatment duration of 3.5 months. Of 21 pts who have had at least one tumor assessment, the ORR was 57.1% (12 PRs) and DCR was 90.5% (12 PRs, 7 SDs). Median PFS has not been reached, and eleven responders remain in response. Treatment-related adverse events (TRAEs) occurred in 53.8% of pts (≥G3 TRAEs occurred in 15.4% [4/26]). Treatment-related SAEs occurred in 15.4% [4/26], and 7.7% of pts [2/26] had drug interruption or discontinuation due to TRAEs. Most common TRAEs (≥15%) were ALT increased, AST increased, hyperthyroidism and hypertension (15.4% each). Conclusions: The combination of penpulimab plus anlotinib as first-line treatment for locally advanced/metastatic NSCLC showed the promising efficacy with a manageable safety profile, thereby suggesting that this combination therapy may be a viable chemo-free treatment strategy for locally advanced/metastatic NSCLC pts. Clinical trial information: NCT03866980.

The fine-mode aerosols (FMA), generally generated from anthropogenic sources, play an essential role in global radiation balance, climate change, atmospheric environment, and human health. However, the FMA retrieval remains a challenge. An improved high resolution FMA retrieval algorithm based on the Spectral Neutrality of Surface Polarized Reflectance (SNOSPR) was developed using polarized satellite data. SNOSPR utilizes a lookup table approach to simultaneously retrieve high spatial resolution FMA parameters, such as FMA optical depth (AODf), Angstrom exponent (AE), and surface polarized reflectance (SPR), without using the surface Bidirectional Polarization Distribution Function (BPDF) model, which may yield relatively more significant errors of SPR estimation in certain surface types. Besides, a new cost function (CF) based on the hypothesis of invariance of SPR was used to select the best retrievals. SNOSPR algorithm was applied to POLDER-3 polarized observation data (i.e., 2010–2012). Inter-comparison between SNOSPR (6 km) and POLDER-3 (L2_LGC,18 km) for two typical cases and monthly averaged AODf products showed a generally consistent spatial distribution, while SNOSPR provided more details, and better coverage over barren and coastal areas at high spatial resolution. Furthermore, all retrieved AODf, AE products of SNOSPR and L2_LGC were validated using AERosol RObotic NETwork (AERONET) measurements. The AODf results showed fine correlation coefficients, i.e., R of 0.9 and 0.89, respectively. However, products of SNOSPR had the expected error range which was higher than that of L2_LGC over all surface types (i.e., 77.3% vs 70.6%), urban (i.e., 76.0% vs 60.6%) and wetland (i.e., 82.4% vs 68.4%). Time-series comparison over grassland showed that SNOSPR had better coverage and more accurate retrievals. Considering AE, both SNOSPR and L2_LGC underestimated its value when validated against AERONET measurements. On the other hand, SPR was retrieved at higher retrieval accuracy by SNOSPR than L2_LGC, which used BPDF. Accuracies of the retrieved AODf improved significantly when multi-directional data was used, especially when the viewing angle number increased from one to four. The uncertainty analysis of spectral neutrality and spatial invariance of SPR was discussed for future improvements of SNOSPR. Last, SNOSPR was applied on Directional Polarimetric Camera (DPC), i.e., a POLDER-like sensor onboard the Chinese Gao Fen-5 satellite. The results in this study demonstrated the effectiveness of the SNOSPR algorithm and its potential for more reliable AODf/SPR retrievals for monitoring local atmospheric pollution and related studies.

Due to rapid industrial development and urbanization, Abuja is characterized with poor and deteriorated air quality. The level of PM2.5 concentrations in Abuja is very high and above the statutory limits; however, the high levels of pollution in Lugbe do not seem to be consistent with local emission sources. This study analyzed the chemical composition of PM2.5 to perform source identification and contributions in Lugbe, Abuja, Nigeria. Sampling in 2016 provided 246 PM2.5 samples at 2 sites across all the four months of sampling. The highest ambient PM2.5 concentration (142 μg m−3) was recorded in winter while the lowest (84 μg m−3) was observed in summer. Chemical mass closure suggested that dust (40.5%) contributed most of the PM2.5 mass. Source apportionment of PM2.5 was performed using positive matrix factorization (PMF) model and six sources were identified. They include mineral dust, crustal dust, vehicle exhaust, secondary nitrate, secondary sulfate, and industrial sources. Crustal dust, vehicle exhaust, and secondary sulfate were the major sources of ambient PM2.5 in Lugbe, contributing 33.3, 29.8, and 18.0%, respectively. The results of 120-h backward trajectories showed that external northeastern region was more dominant in January, while during the remaining three months, southwesterly winds prevailed. The results of bivariate polar plots for most of the factors showed the influence of the southern areas of Lugbe. The study found that there was long-range regional transport of PM2.5 into Lugbe area throughout the four months. Risk assessments revealed that ingestion route was the major exposure pathway for both children and adults. Non-carcinogenic and carcinogenic risk levels were below the acceptable threshold limits. Finally, the results of this study have shown that ambient air quality in Lugbe can be substantially improved by reducing the emissions from crustal dust, vehicle exhaust, and secondary sulfate sources in the external southern regions.

We investigate the influence of the source’s energy fluctuation on both computational ghost imaging and computational ghost imaging via sparsity constraint, and if the reconstruction quality will decrease with the increase of the source’s energy fluctuation. In order to overcome the problem of image degradation, a correction approach against the source’s energy fluctuation is proposed by recording the source’s fluctuation with a monitor before modulation and correcting the echo signal or the intensity of computed reference light field with the data recorded by the monitor. Both the numerical simulation and experimental results demonstrate that computational ghost imaging via sparsity constraint can be enhanced by correcting the echo signal or the intensity of computed reference light field, while only correcting the echo signal is valid for computational ghost imaging.

Pravastatin sodium on triggering receptor expressed on myeloid cell-1 (TREM-1)-mediated inflammation in human peripheral blood mononuclear cells (PBMCs) has been poorly investigated. In this study, we isolated PBMCs from the peripheral blood samples of patients with chronic obstructive pulmonary disease, treated the cells with pravastatin sodium, and determined a concentration at which more than 90% cells could survive. Then we treated cells with 10 ng/ml of lipopolysaccharide, added with 10, 50, 100 μM of pravastatin sodium combined with or without LR-12, a known TREM-1 inhibitor. The expression of TREM-1 was determined by quantitative RT-PCR. The levels of TREM-1, IL-6, and TNF-α in cell culture supernatant were measured with ELISA. Simultaneously, NF-κB signaling pathway-related protein p-p65 and p-IκBα were detected by Western blot assay. Results demonstrated that pravastatin sodium significantly mitigated lipopolysaccharide-stimulated TREM-1 over-expression at mRNA and protein levels dose-dependently. Elevated IL-6 and TNF-α levels changed synchronously. LR-12 inhibited the TREM-1 over-expression and inflammatory factor production but did not show extra synergistic effect to pravastatin. Lipopolysaccharide induced phospho-p65 and -IκBα over-expression was weakened significantly when cells were treated with pravastatin sodium. In conclusion, pravastatin could inhibit TREM-1-medieted inflammation and NF-κB signaling pathway was involved.

Background: Although the significance of D-dimer in cancer patients has been extensively studied and plasma D-dimer levels have been reported to be abnormally high in certain types of lung cancer patients, its prognostic value for small cell lung cancer (SCLC) remains largely unknown. Methods: One hundred and seven newly diagnosed SCLC patients were enrolled in this study. Variables including the clinical features, pre-treatment levels of D-dimer, serum neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) were extracted. The correlations between D-dimer levels and prognosis of the patient were analysed with Kaplan-Meier survival analysis. Results: Plasma D-dimer levels were elevated in 57.01% of patients. Patients with extensive stage disease had higher D-dimer levels compared with those at limited stage. D-dimer levels were positively correlated with NSE and CEA levels. The elevated D-dimer levels were significantly associated with the SCLC-related mortality. Patients with elevated D-dimer levels had a shorter median survival time than those with normal levels, and a significant difference existed between the two groups. Conclusions: Increased D-dimer levels suggested a shorter survival time in SCLC patients. Pre-treatment D-dimer level is useful in estimating the prognosis of patients with SCLC.

The first NIR 3D GISC lidar on a balloon-borne platform, with both transverse and ranging resolutions of higher than 0.5m at over 1.0 km hight, is reported in this paper.

9095 Background: IBI305 is a recombinant humanized anti-VEGF monoclonal antibody, a biosimilar candidate to bevacizumab in analytical and functional comparisons. Pharmacokinetic similarity has been demonstrated in healthy males. Here we present primary efficacy and safety results from a phase 3 comparative study in non-small cell lung cancer (NSCLC). Methods: In this double-blind, active-controlled study, subjects with advanced non-squamous NSCLC on first-line treatment with carboplatin and paclitaxel were randomized (1:1) to IBI305 or bevacizumab (15 mg/kg IV Q3W). After six cycles, patients were on maintenance treatment with IBI305 or bevacizumab (7.5 mg/kg IV Q3W) till progression. Clinical equivalence of the primary endpoint, confirmed objective response rate (ORR) was evaluated by comparing the 2-sided 90% confidence interval (CI) of the risk ratio (RR) between study arms with the prespecified margin (0.75, 1.33). Results: A total of 450 subjects were randomized (IBI305: n = 224; bevacizumab: n = 226). Baseline characteristics were well balanced between treatment arms. ORR evaluated by Independent Radiological Review Committee (IRRC) in full analysis set (FAS) was 44.3% (98/221) for IBI305 and 46.4% (102/220) for bevacizumab; the RR for ORR was 0.95 (90% CI: 0.803, 1.135). Sensitive analysis result on RRs of ORR in Intention to Treat (ITT) population (IBI305: n = 224; bevacizumab: n = 226) and other analysis set were consistent and all within the prespecified equivalence margin. The medium PFS were 8.4 months for IBI305 and 8.3 months for bevacizumab and duration of response (DOR) was also similar in both arms. Treatment-emergent adverse events (TEAEs) were well balanced between treatment arms and consistent with the known adverse event profile of bevacizumab. Patients developing binding antibodies were 0.5% in the IBI305 arm vs 0% in the bevacizumab arm; no subject tested positive for neutralizing antibodies. Conclusions: This is the first released phase 3 clinical study with maintenance treatment for bevacizumab biosimilar in NSCLC patients till now. The comparative study met its predefined primary endpoint that the RR for confirmed ORR was within the prespecified equivalence margin. There was no significant difference between the two arms in safety profile and immunogenicity. Clinical trial information: NCT02954172.