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Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide. The use of a combination of chemotherapy drugs and zinc oxide nanoparticles (ZnO-NPs), which have proven to induce tumor-selective cell death, reduce the drug resistance and reduce the side effects in vitro. In the present study, we developed ZnO-NPs loaded with both cisplatin (Cp) and gemcitabine (Gem) (ZnO-NPs(Cp/Gem)), then the morphologies and the size distribution of ZnO-NPs(Cp/Gem) particles were observed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Also, MTT, western blot and Annexin V-PI were used to assess the anti-tumor role of ZnO-NPs(Cp/Gem) in A549 cells. The viability for A549 cells showed a significant decrease in the ZnO NPs(Cp/Gem) group, respectively relative to Cp, Gem, the combination of Cp and Gem (Cp+Gem), and ZnO-NPs loaded with Cp (ZnO-NPs(Cp)) or Gem (ZnO-NPs(Gem)). Furthermore, ZnO-NPs(Cp/Gem) remarkably enhanced the apoptosis-promoting effect of Cp and Gem in A549 cells. The xenograft model showed that Zno-NPS (Cp/Gem) significantly enhanced the inhibition of Cp and Gem on tumor formation. The above results suggested that therapy of NSCLC with ZnO-NPs(Cp/Gem) could enhance the cytotoxic action of chemotherapeutic agents synergistically, indicating a promising potential for ZnO-NPs in antitumor applications.

Aim: Several members of secreted frizzled-related protein (SFRP) are involved in the process of myocardial ischemia-reperfusion injury. However, little is known about the role of SFRP5 in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: In this cross-sectional study, 85 patients with first-time anterior STEMI who underwent timely primary percutaneous coronary intervention (PCI) and 35 patients without coronary artery disease (CAD) were enrolled. Serum SFRP5 levels were measured using an enzyme-linked immunosorbent assay kit. Patients with STEMI were divided into low-SFRP5 and high-SFRP5 groups according to their median baseline serum SFRP5 levels. To evaluate cardiac function and structure after infarction, the left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume (LVEDV) were measured using echocardiography. The associations between changes in LVEF and reduced LVEF (≤ 50%) and clinical variables were determined by univariate and multivariate analyses. Results: Baseline serum SFRP5 levels were significantly higher in patients with STEMI than in those without CAD (23.3 ng/mL vs 19.8 ng/mL, P = 0.008), although they decreased over time. Also, baseline serum SFRP5 levels were inversely correlated with peak hypersensitive cardiac troponin I (hs-cTnI) levels (r = −0.234, P = 0.025) and peak hypersensitive C-reactive protein (hs-CRP) levels (r = −0.262, P = 0.015). A multivariate linear regression model showed that changes in LVEF were positively correlated with serum SFRP5 levels at baseline (β = 0.249, 95% confidence interval (CI) 0.018–0.245, P = 0.024) and 24 h after admission (β = 0.220, 95% CI 0.003–0.264, P = 0.045). At 3 months, LVEF in patients with high SFRP5 levels was significantly improved over baseline [(60.8 ± 7.1) % vs (56.1 ± 7.5) %, P = 0.001]. LVEF was also significantly higher in patients with high SFRP5 levels than in those with low at the 3-month follow-up [(60.8 ± 7.1) % vs (56.8 ± 8.9) %, P = 0.028]. Consequently, high serum SFRP5 levels at baseline were associated with a decreased risk of reduced LVEF at 3 months, independent of peak hs-cTnI and baseline cardiac function (hazard ratio 0.190, 95% CI 0.036–0.996; P = 0.049). Conclusions: High serum SFRP5 levels measured during the acute phase of STEMI were significantly associated with promoting myocardial recovery at an early phase following primary PCI, suggesting that SFRP5 is a potential therapeutic target in acute STEMI.

Additional file 1: Figure S1. Study flow-chart. Table S1. Lesion-level predictors for myocardial ischemia in univariate and multivariate analyses.

Background We aimed to investigate the association of lesion-specific epicardial adipose tissue (EAT) volume and density with the presence of myocardial ischemia. Methods We enrolled 45 patients (55 lesions) with known or suspected coronary artery disease who underwent coronary computed tomography angiography (CTA) followed by invasive fractional flow reserve (FFR) assessment within 30 days. EAT volume (index) and density in patient-, vessel- and lesion-level were measured on CTA images. Lesion-specific ischemia was defined as a lesion with stenosis diameter > 90% or FFR ≤0.80. Multivariate analysis determined the independent association of EAT parameters with lesion-specific ischemia. Results Mean age of the patients was 60 years, and 75% were male. Overall, 55.6% of patients had ischemic lesions and a mean FFR baseline value of 0.82 ± 0.10. Total EAT volume index was significantly higher in patients with functionally or anatomically significant stenosis. Specifically, peri-lesion EAT volume index, not the density, was positively correlated with lesion-specific ischemia independent of luminal stenosis and plaque characteristics (hazard ratio 1.56, 95% confidence interval 1.04–2.33, P = 0.032; per 0.1 ml/m2 increase). Moreover, peri-lesion EAT volume was negatively correlated with lesion FFR values, whereas total EAT volume was positively correlated with fat accumulation and glucose metabolism. In addition, there was no association of EAT volume or density with myocardial ischemia in vessel-level analysis. Conclusions Lesion-specific EAT volume index, but not density, seems positively and independently associated with myocardial ischemia, while its incremental diagnostic value of lesion-specific ischemia should be further investigated.

BACKGROUND: Data on immuno-oncology agents in Chinese patients are limited despite a need for new therapies. We evaluated the efficacy and safety of nivolumab in a predominantly Chinese patient population with previously treated non-small-cell lung cancer (NSCLC). METHODS: CheckMate 078 was a randomised, open-label, phase 3 clinical trial enrolling patients from China, Russia, and Singapore with NSCLC whose disease progressed during/after platinum-based doublet chemotherapy. Patients (N=504) were included regardless of tumour histology and programmed death ligand 1 (PD-L1) expression; those with EGFR/ALK alterations were excluded. Patients were randomised 2:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks), stratified by performance status, histology, and tumour PD-L1 expression. The primary endpoint was overall survival (OS); secondary endpoints included objective response rate (ORR) and progression-free survival. FINDINGS: OS was significantly improved with nivolumab (n=338) versus docetaxel (n=166); median OS (95% CI), 12·0 (10·4-14·0) versus 9·6 (7·6- 11·2) months, respectively; hazard ratio (97·7% CI), 0·68 (0·52-0·90); p=0·0006. ORR was 17% with nivolumab versus 4% with docetaxel; median duration of response was not reached versus 5·3 months. Minimum follow-up was 8·8 months. The frequency of grade ≥3 treatment-related adverse events was 10% with nivolumab and 48% with docetaxel. INTERPRETATION: This is the first phase 3 study in a predominantly Chinese population reporting results with a PD-1 inhibitor. In this population with previously treated advanced NSCLC, nivolumab improved OS versus docetaxel. Results were consistent with global CheckMate 017 and 057 studies. CLINICAL TRIAL NUMBER: CheckMate 078 is registered on ClinicalTrials.gov, number NCT02613507. FUNDING STATEMENT: The study was funded by Bristol-Myers Squibb. Bristol-Myers Squibb was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. DECLARATION OF INTERESTS: Y-LW has received grants from Roche; has received personal fees from AstraZeneca, Eli Lilly, Pfizer, Roche, and Sanofi; and has received non-financial support from AstraZeneca. JW has received non-financial support from AstraZeneca. TM has received grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Eisai, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, SFJ Pharmaceuticals, Taiho, Takeda, and XCovery and has received personal fees from ACEA Biosciences, AstraZeneca, Boehringer Ingelheim, BristolMyers Squibb, Celgene, ChiMed, Clovis Oncology, Eli Lilly, Fishawack Facilitate Ltd, Ignyta Inc, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, OncoGenex, Pfizer, Roche/Genentech, SFJ Pharmaceuticals, Taiho, Takeda, and Vertex. CB and J Cai are employees of Bristol-Myers Squibb. All other authors report no competing interests. ETHICS APPROVAL STATEMENT: The study was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonisation guidelines on good clinical practice. The study protocol was approved by an institutional review board or independent ethics committee at each site. An independent data monitoring committee monitored the activity and safety of nivolumab versus docetaxel throughout the study

Purpose To compare supportive care costs associated with second-line chemotherapy for advanced non-squamous non-small cell lung cancer (advNS-NSCLC) in Chinese patients. Methods This retrospective cohort study included patients receiving pemetrexed or docetaxel-based second-line chemotherapy for advNS-NSCLC in four Chinese hospitals from 2007 to 2012. The best matched pairs between pemetrexed and other regimens were identified using propensity score methods for head-to-head comparisons of supportive care costs per treatment cycle. Linear regression analyses were performed to rank log10 scale of supportive care costs per treatment cycle associated with chemotherapy by tumor response and hematologic toxicity. Results 384 patients were included to create propensity score-matched treatment groups for pemetrexed singlet versus docetaxel singlet, platinum/pemetrexed, and platinum/docetaxel, respectively. Pemetrexed singlet was associated with significantly less supportive care costs per treatment cycle than the two doublets (platinum/pemetrexed: median difference −RMB 9,877, p = 0.003; platinum/docetaxel: median difference −RMB 8,370, p = 0.009; 1 RMB = 0.16 USD) but not docetaxel singlet in matched patients. Of the four studied chemotherapy regimens, pemetrexed singlet was associated with the lowest log10 scale of supportive care costs per treatment cycle in patients with tumor control (coefficient relative to docetaxel singlet −1.049, p

Jianhua Chen,1 Shengqi Wu,2 Chenping Hu,3 Yicheng Yang,4 Narayan Rajan,5 Yun Chen,4 Canjuan Yang,6 Jianfeng Li,6 Wendong Chen7 1Department of Medical Oncology, 2Department of Research and Education, Hunan Province Tumor Hospital, 3Department of Respiratory, Xiangya Hospital, Central South University, Changsha, Hunan, 4Lilly Suzhou Pharmaceutical Co., Ltd. Shanghai Branch, Shanghai, People's Republic of China; 5Global Health Outcomes Research, Eli Lilly and Co, Indianapolis, IN, USA; 6Division of Health Outcome Research, Normin Health Changsha Representative Office, Changsha, Hunan, People's Republic of China; 7Normin Health, Toronto, ON, Canada Objective: The objective of this study was to compare hospital costs per treatment cycle (HCTC) for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer (AdvNS-NSCLC) in Chinese patients. Methods: Patients receiving platinum-based doublets in the first-line setting for AdvNS-NSCLC from 2010 to 2012 in two Chinese tertiary hospitals were identified to create the retrospective study cohort. Propensity score methods were used to create matched treatment groups for head-to-head comparisons on HCTC between pemetrexed–platinum and other platinum-based doublets. Multiple linear regression analyses were performed to rank studied platinum-based doublets for their associations with the log10 scale of HCTC for nonchemotherapy drugs and nondrug care. Results: Propensity score methods created matched treatment groups for pemetrexed–platinum versus docetaxel–platinum (61 pairs), paclitaxel–platinum (39 pairs), gemcitabine–platinum (93 pairs), and vinorelbine–platinum (73 pairs), respectively. Even though the log10 scale of HCTC for nonchemotherapy drugs and nondrug care associated with pemetrexed–platinum was ranked lowest in all patients (coefficient –0.174, P=0.015), which included patients experiencing any hematological adverse events (coefficient –0.199, P=0.013), neutropenia (coefficient –0.426, P=0.021), or leukopenia (coefficient –0.406, P=0.001), pemetrexed–platinum had the highest total HCTC (median difference from RMB 1,692 to RMB 7,400, P

The incidence of type II diabetes mellitus (T2DM) is increasing worldwide and affecting the quality of people's life. This study was designed to evaluate the effect of care intervention on body weight and glycemic parameters in obese T2DM patients. One hundred twenty-six obese T2DM cases were randomly divided into 2 groups. Patients in control group received conventional care, while patients in the intervention group received dietary, exercise, and psychology interventions on the basis of conventional care. Twelve months follow-up was performed to compare the changes of body weight and glycemic parameters in the 2 groups. There were 119 patients completing the research, 60 in the intervention group and 59 in control group. The levels of fasting plasma glucose (FPG), 2 hours postprandial blood glucose (PBG2 h), hemoglobin A1c (HbA1c), and aldose reductase (AR) were all significantly decreased (all, P

Background Real-world evidence lacks for clinical effectiveness and clinical toxicity associated with platinum-based doublets in the first-line setting for advanced non-squamous non-small cell lung cancer (advNS-NSCLC) in Chinese patients. Methods Patients receiving first-line chemotherapy for advNS-NSCLC in four Chinese tertiary care hospitals from 2007 to 2012 were retrospectively identified for chart review. Propensity score methods created best matched pairs for platinum/pemetrexed versus other platinum-based doublets for head-to-head comparisons of early treatment discontinuation (completed treatment cycles