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Background Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small‐scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first‐line treatment in locally advanced or metastatic LSCC. Methods Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression‐free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45‐Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses. Results The median duration of follow‐up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF‐α, IFN‐γ, IL‐6, and IL‐8, demonstrating an overlapping trend. Conclusion The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen., Cisplatin plus Lipusu (LP) regimen has comparable efficacy and more favorable toxicity profiles compared with cisplatin plus gemcitabine (GP) regimen for patients with advanced LSCC. The study also demonstrated that LP had a significant impact on the levels of plasma cytokines and a spectrum of cytokines were associated with clinical benefit in patients who received LP. Thus, our results provided a new option for patients with advanced LSCC.

Pulmonary hypertension (PH) is prevalent in patients with obstructive sleep apnea (OSA) syndrome, and coexistence of PH and OSA indicates a worse prognosis and higher mortality. Chronic intermittent hypoxia (CIH) is the key pathogenesis of OSA. Also, microRNA-223 (miR-223) plays a role in the regulation of CIH-induced PH process. However, the detailed mechanism of CIH inducing PH is still unclear. This study aimed to investigate the pathological process of CIH associated PH and explore the potential therapeutic methods. In this study, adult Sprague-Dawley rats were exposed to CIH or normoxic (N) conditions with 2-methoxyestradiol (2-Me) or vehicle treatment for 6 weeks. The results showed that 2-Me treatment reduced the progression of pulmonary angiogenesis in CIH rats, and alleviated proliferation, cellular migration, and reactive oxygen species formation was induced by CIH in pulmonary artery smooth muscle cells (PASMCs). CIH decreased the expression of miR-223, whereas 2-Me reversed the downregulation of miR-223 both in vivo and in vitro. Furthermore, the antiangiogenic effect of 2-Me observed in PASMCs was abrogated by miR-223 inhibitor, while enhanced by miR-223 mimic. These findings suggested that miR-223 played an important role in the process of CIH inducing PH, and 2-Me might reverse CIH-induced PH via upregulating miR-223.

Gastric aspiration lung injury is one of the most common clinical events. This study investigated the effects of bone‐marrow‐derived mesenchymal stem cells (BMSCs) on combined acid plus small non‐acidified particle (CASP)‐induced aspiration lung injury. Enhanced green fluorescent protein (EGFP +) or EGFP − BMSCs or 15d‐PGJ 2 were injected via the tail vein into rats immediately after CASP‐induced aspiration lung injury. Pathological changes in lung tissues, blood gas analysis, the wet/dry weight ratio (W/D) of the lung, levels of total proteins and number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) were determined. The cytokine levels were measured using ELISA. Protein expression was determined by Western blot. Bone‐marrow‐derived mesenchymal stem cells treatment significantly reduced alveolar oedema, exudation and lung inflammation; increased the arterial partial pressure of oxygen; and decreased the W/D of the lung, the levels of total proteins and the number of total cells and neutrophils in BALF in the rats with CASP‐induced lung injury. Bone‐marrow‐derived mesenchymal stem cells treatment decreased the levels of tumour necrosis factor‐α and Cytokine‐induced neutrophil chemoattractant (CINC)‐1 and the expression of p‐p65 and increased the levels of interleukin‐10 and 15d‐PGJ 2 and the expression of peroxisome proliferator‐activated receptor (PPAR)‐γ in the lung tissue in CASP‐induced rats. Tumour necrosis factor‐α stimulated BMSCs to secrete 15d‐PGJ 2. A tracking experiment showed that EGFP + BMSCs were able to migrate to local lung tissues. Treatment with 15d‐PGJ 2 also significantly inhibited CASP‐induced lung inflammation and the production of pro‐inflammatory cytokines. Our results show that BMSCs can protect lung tissues from gastric aspiration injury and inhibit lung inflammation in rats. A beneficial effect might be achieved through BMSC‐derived 15d‐PGJ 2 activation of the PPAR‐γ receptor, reducing the production of proinflammatory cytokines.

Although crizotinib has demonstrated promising efficacy and acceptable toxicity in patients with advanced non‐small cell lung cancer (NSCLC), the available evidence in Chinese populations is currently limited. This study compared the progression‐free survival (PFS) of Chinese patients with anaplastic lymphoma kinase (ALK)‐positive, advanced lung adenocarcinoma who received first‐line crizotinib therapy with that of patients who received first‐line standard chemotherapy, and also the PFS benefit of first‐line versus second‐line crizotinib treatment. Data on 80 patients with ALK‐positive, advanced lung adenocarcinoma who received crizotinib or standard chemotherapy as first‐line treatments between June 2013 and December 2014 were retrospectively collected; 26 of the patients received crizotinib as second‐line therapy after progressive disease (PD) occurred on first‐line chemotherapy. Tumor responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The median PFS was 13.3 months (95% CI: 6.5–20.0 months) in patients who received first‐line crizotinib as compared with 5.4 months (95% CI: 4.4–6.5 months) in patients who received first‐line standard chemotherapy (adjusted hazard ratio for progression or death with crizotinib, 0.20; 95% CI: 0.11–0.36; P

Efficient separation and enrichment of low-abundance glycopeptides from complex biological samples is the key to the discovery of disease biomarkers. In this work, a new material was prepared by coating copper tetra(N-carbonylacrylic) aminephthalocyanine and iminodiacetic acid onto poly(glycidyl methacrylate-pentaerythritol triacrylate) monolith. The monolith was applied to polymer monolithic microextraction for specific capture of glycopeptides coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The developed monolith exhibited satisfactory efficiency for glycopeptide enrichment with high selectivity and detection sensitivity. When the tryptic digest of immunoglobulin G was used as the sample, total 24 glycopeptides were identified and the detection limit was determined as 5 fmol. When the approach was applied to the analysis of glycopeptides in the mixture of bovine serum albumin and immunoglobulin G (100:1, m/m) digests, 16 glycopeptides could still be observed. Moreover, the monolith was successfully applied to the selective enrichment of glycopeptides from human serum digests, exhibiting great practicability in identifying low-abundance glycopeptides in complex biological samples.

Background Adaptive servoventilation (ASV) is a new therapeutic modality to treat sleep-disordered breathing (SDB) especially for central sleep apnoea associated with Cheyne–Stokes respiration, whereas the role of ASV in SDB patients with heart failure (HF) is controversial. The purpose of this study was to evaluate the effects of ASV on these patients through a meta-analysis of published data. Methods A comprehensive literature search was performed to identify studies focused on ASV through databases, including PubMed, Medline, Embase, Cochrane Library and Web of science from 1950 to 2014. Parallel randomised controlled trials which compared ASV to other controls in HF and SDB patients with extractable data were meet our inclusion criteria. Random effects meta-analysis models were applied using RevMan 5.2. Results Seven studies involving 301 patients were recruited in the meta-analysis. The weighted mean difference in apnoea hyponea index (−17.73 events/h, 95% CI, −21.85 to −2.94) and left ventricular ejection fraction (MD: 4.68, 95% CI, 2.74–6.63) both favored ASV compared to control conditions. The urinary noradrenaline level (MD: −32.18, 95%CI: −44.07 to −20.09) was decreased, while the exercise capacity measured by 6-min walk distance (MD: 41.26, 95% CI, 17.06–65.45) was improved after ASV treatment. Whereas neither left ventricular end-diastolic diameter (LVEDD) nor Epworth sleepiness-scale score (ESS) significantly changed after ASV therapy. Conclusions ASV is superior to other therapy, as it can result in good consequences for patients with SDB and improve their prognosis in cardiac function. Further studies will still be needed to assess the benefit of it.

An efficient chemoenzymatic process for the synthesis of azoxybenzenes was developed. A peracid was generated in situ by Novozym 435, and then a range of anilines were oxidized by the produced peracid to afford azoxybenzenes in yields ranging from 63.1 to 94.1 %. This method expands the application of lipase in organic synthesis and provides an alternative method for the synthesis of azoxybenzenes.

Background and Aims Low-dose computed tomography (LDCT) has been proposed to be a new screening method to discover lung cancers in an early stage, especially those patients who are in a high risk of lung cancer. The primary objective of this meta-analysis is to systematically review the effect of LDCT on screening for lung cancers among the risky population who are older than 49 years old and with smoking exposure. Methods We searched randomized controlled clinical trials (RCTs) about comparing LDCT and chest X-ray or usual caring from MEDLINE, EMBASE, and the Cochrane Library, Web of Knowledge and Springerlink databases (January 1994 to September 2013). Results Nine RCTs met criteria for inclusion. Screening for lung cancer using LDCT resulted in a significantly higher number of stage I lung cancers [odds ratio (OR) 2.15, 95% confidence interval (CI) 1.88–2.47], higher number of total lung cancers (OR 1.31, 95% CI 1.20–1.43) than the control. Four of the nine studies indicated that the screening method did not decrease all-cause mortality (OR 0.96, 95% CI 0.90–1.02), but decreased lung cancer-specific mortality (OR 0.84, 95% CI 0.74–0.96). Five studies showed that LDCT had higher false-positive rates (OR 8.7, 95% CI 7.43–10.19) than the group of control. Conclusion Among the risky population, LDCT screening find out more stage I lung cancers and total lung cancers compared with chest X-ray or no screening, and also shows advantages in decreasing lung cancer-specific mortality, but the screening method does not decrease all-cause mortality and have a higher false-positive rates in diagnosis.

Ultrasound has been successfully adopted to improve the biocatalytic properties of APE1547 (a novel esterase from the archaeon Aeropyrum pernix K1) in the resolution of ibuprofen. After optimizing the conditions (ultrasound power, 200 W; temperature, 35 °C), the best biocatalytic performance of APE1547 (enzyme activity, 5.39 µmol/H/mg; E value, 130.8) was obtained. Compared with the conventional reaction in an orbital shaker, the enzyme activity was significantly enhanced about 90-fold, and the enantioselectivity was enhanced about fourfold after an ultrasound. The results of scanning electron microscopy clearly indicated that the activation effect of ultrasound on APE1547 originated mainly in the morphological change of the enzyme powder. Both lower particle size and conformational change of APE1547 under ultrasound might be helpful to enhance the enantioselectivity. In addition, APE1547 kept its best performance under the low-power ultrasound for at least five reaction cycles.

Background Sunitinib is an oral multitargeted tyrosine kinase inhibitor (TKI) exhibiting antiagiogenic and antitumor effects. Objective To evaluate the efficacy and potential toxicity of sunitinib therapy in advanced non-small cell lung cancer (NSCLC) patients in China. Methods From January 2009 to August 2011, 30 patients with stage IV NSCLC, who were pretreated with the epidermal growth factor receptor (EGFR)-TKIs and then received sunitinib, were retrospectively reviewed. Univariate and multivariate Cox proportional hazard regression analysis was performed to determine the potential prognostic risk factors influencing NSCLC survival. Results The median progression-free survival (PFS) and median overall survival (OS) of all 30 treated patients was 1.25 months [95% confidence interval (CI): 0.90–1.9 months] and 3.40 months (95% CI: 3.00–6.80 months), respectively. Cox regression analysis suggested that Eastern Cooperative Oncology Group (ECOG) performance status (PS) is predictive of both PFS (P = 0.001) and OS (P

An efficient chemoenzymatic process for the synthesis of azoxybenzenes was developed. A peracid was generated in situ by Novozym 435, and then a range of anilines were oxidized by the produced peracid to afford azoxybenzenes in yields ranging from 63.1 to 94.1 %. This method expands the application of lipase in organic synthesis and provides an alternative method for the synthesis of azoxybenzenes.

A practical approach for rapidly screening antioxidants against superoxide anion radicals from complex mixtures was developed based on the quantitative difference in active compounds before and after their reaction. To test the effectiveness of the approach, seven flavonoids with antioxidative properties were investigated both individually and in a mixture. Using the approach, antioxidants could be rapidly separated and screened with a ranked order of activities in the meantime. The radical scavenging activities were in the following order: quercetin > kaempferol > fisetin > puerarin > luteolin > rutin > baicalein. The order of activity was conducted by comparing the scavenging ratio of the antioxidant, which was completely consistent with the results obtained from the traditional electronic spin resonance. Then, the method was successfully applied to black tea extracts. This approach is fast and convenient for screening, isolating, and analyzing potential antioxidants from a mixture with good quantitative and reproducible ability.

BACKGROUND: Grapes and red wines are rich sources of phenolic compounds such as anthocyanins, catechins, flavonols and stilbenes, most of which are potent antioxidants showing cardioprotective properties. We first isolated scirpusin A, a hydroxystilbene dimer, from a wine grape of Xinjiang, and studied its antioxidant activity. RESULTS: Reactive oxygen species scavenging effects and the protection against reactive singlet oxygen-induced DNA damage of scirpusin A have been investigated in our experiments. The concentration of scirpusin A required to inhibit 50% of 1O2 generation was 17 µmol L−1, while addition of scirpusin A at 140 µmol L−1 caused complete inhibition. Further kinetic study revealed that the reaction of Scirpusin A with singlet oxygen has an extremely high rate constant (ka = 4.68 × 109 L mol−1 s−1). Scirpusin A (140 µmol L−1) exhibited significant inhibition effects on pBR322 DNA breakage. However, scavenging effects of scirpusin A on superoxide anion O2•− and hydroxyl radical ·OH were not potent as the inhibitor rates at a concentration of 1400 µmol L−1 were 28.83% and 19.5%, respectively. CONCLUSION: The present study shows that scirpusin A is a selective quencher of singlet oxygen and a protector against reactive singlet oxygen-induced pBR322 DNA damage at very low concentrations. Copyright © 2010 Society of Chemical Industry

Laetevirenols F (1) and G (2), two novel stilbene tetramers with an unprecedented skeleton, were isolated from Parthenocissus laetevirens. Their structures were elucidated by spectroscopic analysis, including 1D- and 2D-NMR experiments, and their possible biogenetic pathway was discussed. In addition, both compounds were determined to be potent singlet-oxygen quenchers by electron paramagnetic resonance (EPR) experiments, which highlights their potential pharmacological applications in singlet oxygen mediated diseases.

Preparative high-speed counter-current chromatography (HSCCC) was successfully applied to the isolation and purification of three stilbene oligomers from Vitis chunganeniss using stepwise elution with a pair of two-phase solvent systems composed of n-hexane-ethyl acetate-methanol-water at (2:5:2:5, v/v) and (1:2:1:2, v/v). The preparative HSCCC separation was performed on 800 mg of crude sample yielding hopeaphenol (21.1 mg), amurensin G (37.2 mg) and vitisin A (95.6 mg) in a one-step separation, with purities over 95% as determined by HPLC. The structures of these three compounds were identified by MS, (1)H NMR and (13)C NMR. In addition, their antioxidant activities were screened by DPPH assay, where vitisin A showed strong antioxidant activity. Further EPR experiments with spin-trapping technique demonstrated that vitisin A is a potent and selective singlet oxygen quencher, which may be used in singlet oxygen-mediated diseases as a pharmacological agent.

The method is efficient, environmentally friendly and extends the phenomenon of enzyme promiscuity.