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Kaplan-Meier curves for progression-free survival in subgroups.

Purpose:Preclinical and retrospective studies suggested a role for metformin in sensitizing patients who have diabetes with non–small cell lung cancer (NSCLC) to EGFR tyrosine kinase inhibitors (TKIs). We therefore examined its effects in combination with gefitinib in patients without diabetes harboring EGFR mutations (EGFRm).Patients and Methods:A total of 224 patients without diabetes with treatment-naïve stage IIIB–IV EGFRm NSCLC were randomly assigned in a 1:1 ratio to receive gefitinib plus either metformin or placebo. The primary endpoint was progression-free survival (PFS) rate at 1 year and secondary endpoints included overall survival (OS), PFS, objective response rate (ORR), and safety. Serum levels of IL6 were also examined in an exploratory analysis.Results:The median duration of follow-up was 19.15 months. The estimated 1-year PFS rates were 41.2% [95% confidence interval (CI), 30.0–52.2] with gefitinib plus metformin and 42.9% (95% CI, 32.6–52.7) with gefitinib plus placebo (P = 0.6268). Median PFS (10.3 months vs. 11.4 months) and median OS (22.0 months vs. 27.5 months) were numerically lower in the metformin group, while ORRs were similar between the two arms (66% vs. 66.7%). No significant treatment group differences were detected across all subgroups with respect to PFS, including those with elevated levels of IL6. Metformin combined with gefitinib resulted in a remarkably higher incidence of diarrhea compared with the control arm (78.38% vs. 43.24%).Conclusions:Our study showed that addition of metformin resulted in nonsignificantly worse outcomes and increased toxicity and hence does not support its concurrent use with first-line EGFR-TKI therapy in patients without diabetes with EGFRm NSCLC.

Aluminum (Al) stress in acidic soils has severe negative effects on crop productivity. In this study, the alleviating effect and related mechanism of malate on Al stress in quinoa (Chenopodium quinoa) seedlings were investigated. The findings indicated that malate alleviated the growth inhibition of quinoa seedlings under Al stress, maintained the enzymatic and nonenzymatic antioxidant systems, and aided resistance to the damage caused by excessive reactive oxygen species (ROS). Under Al stress, malate significantly increased the contents of chlorophyll and carotenoids in quinoa shoots by 103.8% and 240.7%, and significantly increased the ratios of glutathione (GSH)/oxidized glutathione (GSSG), and ascorbate (AsA)/dehydroascorbate (DHA) in roots by 59.9% and 699.2%, respectively. However, malate significantly decreased the superoxide radical (O

Drought stress is a key agricultural problem that restricts plant development and crop yield. Research on quinoa (Chenopodium quinoa), a nutrient-rich crop with strong stress resistance, has been limited in terms of the molecular regulation of its adaptation to drought stress. This study identified the zinc finger-homeodomain (ZF-HD) family in quinoa and a drought-responsive Chenopodium quinoa ZF-HD14 (CqZF-HD14) through expression profiles. Transient overexpression of CqZF-HD14 promotes photosynthetic pigment accumulation under drought stress, strengthens the antioxidant system, and in turn enhances drought tolerance. Comprehensive genome-wide family analysis and expression profiling identified CqNAC79 and CqHIPP34 regulated by CqZF-HD14, and their interactions were further determined by bimolecular fluorescence complementation (BIFC). Moreover, physiological and biochemical analyses and transient overexpression also revealed that CqNAC79 and CqHIPP34 resist drought by promoting the accumulation of photosynthetic pigments and maintaining antioxidant capacity under drought stress. The synergistic effect of CqZF-HD14 with CqNAC79 or CqHIPP34 further enhanced the drought tolerance of quinoa seedlings. Taken together, the results indicate that CqZF-HD14, CqNAC79 and CqHIPP34 may be important contributors to the drought tolerance regulatory network in quinoa, and these findings add new members to the drought tolerance gene pool.

High altitude (HA) exposure has been considered as a cardiac stress and might impair ventricular diastolic function. Atrial contraction is involved in ventricular passive filling, however the atrial performance to HA exposure is poorly understood. This study aimed to evaluate the effect of short-term HA exposure on bi-atrial function. Physiological and 2D-echocardiographic data were collected in 82 healthy men at sea level (SL, 400 m) and 4100 m after an ascent within 7 days. Atrial function was measured using volumetric and speckle-tracking analyses during reservoir, conduit and contractile phases of cardiac cycle. Following HA exposure, significant decreases of reservoir and conduit function indexes were observed in bi-atria, whereas decreases of contractile function indexes were observed in right atrium (RA), estimated via RA active emptying fraction (SL 41.7 ± 13.9% vs. HA 35.4 ± 12.2%, p = 0.001), strain during the contractile phase [SL 13.5 (11.4, 17.8) % vs. HA 12.3 (9.3, 15.9) %, p = 0.003], and peak strain rate during the contractile phase [SL − 1.76 (− 2.24, − 1.48) s−1 vs. HA − 1.57 (− 2.01, − 1.23) s−1, p = 0.002], but not in left atrium (LA). In conclusion, short-term HA exposure of healthy individuals impairs bi-atrial performance, mostly observed in RA. Especially, atrial contractile function decreases in RA rather than LA, which seems not to compensate for decreased ventricular filling after HA exposure. Our findings may provide a novel evidence for right-sided heart dysfunction to HA exposure. Supplementary Information The online version of this article (10.1007/s10554-021-02173-8) contains supplementary material, which is available to authorized users.

Cadmium (Cd) has a serious negative impact on crop growth and human food security. This study investigated the alleviating effect of β-cyclocitral, a potential heavy metal barrier, on Cd stress in quinoa seedlings and the associated mechanisms. Our results showed that β-cyclocitral alleviated Cd stress-induced growth inhibition in quinoa seedlings and promoted quinoa seedling root development under Cd stress. Moreover, it maintained the antioxidant system of quinoa seedlings, including the enzymatic, i.e., superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), and nonenzymatic, i.e., reduced glutathione (GSH) and ascorbic acid (ASA), antioxidants, which eliminate the damage from excessive reactive oxygen species (ROS). Our results showed that β-cyclocitral could reduce the amount of Cd absorbed by roots. Furthermore, we systematically identified five transporter families from the quinoa genome, and the RT-qPCR results showed that ZIP, Nramp and YSL gene families were downregulated by β-cyclocitral to reduce Cd uptake by roots. Thus, β-cyclocitral promoted the growth, photosynthetic capacity and antioxidant capacity of the aboveground parts of quinoa seedlings. Taken together, these results suggested that the β-cyclocitral-induced decrease in Cd uptake may be caused by the downregulation of several selected transporter genes.

BACKGROUND The authors built a model for lung cancer diagnosis previously based on the blood biomarkers progastrin-releasing peptide (ProGRP), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and cytokeratin 19 fragment (CYFRA21-1). In the current study, they examined whether modification of the model to include relevant clinical information, risk factors, and low-dose chest computed tomography screening would improve the performance of the biomarker panel in large cohorts of Chinese adults. METHODS The current study was a large-scale multicenter study (ClinicalTrials.gov identifier NCT01928836) performed in a Chinese population. A total of 715 participants were enrolled from 5 regional centers in Beijing, Henan, Nanjing, Shanghai, and Chongqing between October 2012 and February 2014. Serum biomarkers ProGRP, CEA, SCC, and CYFRA21-1 were analyzed on the ARCHITECT i2000SR. Relevant clinical information was collected and used to develop a patient risk model and a nodule risk model. RESULTS The resulting patient risk model had an area under the receiver operating characteristic (ROC) curve of 0.7037 in the training data set and 0.7190 in the validation data set. The resulting nodule risk model had an area under the ROC curve of 0.9151 in the training data set and 0.5836 in the validation data set. Moreover, the nodule risk model had a relatively higher area under the ROC curve (0.9151 vs 0.8360; P = 0.001) compared with the American College of Chest Physician model in patients with lung nodules. CONCLUSIONS Both the patient risk model and the nodule risk model, developed for the early diagnosis of lung cancer, demonstrated excellent discrimination, allowing for the stratification of patients with different levels of lung cancer risk. These new models are applicable in high-risk Chinese populations. Cancer 2018;124:262-70. © 2017 American Cancer Society.

In order to further improve the accuracy of digital core modeling, a new hybrid method was proposed to construct the dual pore 3-D digital core with high precision. First of all, 3-D macro-pore digital cores were constructed by micro-CT. Secondly, based on the high-resolution 2-D scanning electron microscopy images of rock cores, micro-pore digital cores were constructed by simulated annealing method. And then, a superposition method was used to construct the digital core which could describe different pore characteristics. Finally, pore structures of digital cores were compared, and lattice Boltzmann method was used to analyze the percolation properties. The results show that the carbonate dual pore digital core constructed by the new hybrid method has a high accuracy, which can capture the pore properties of both macro-pore and micro-pore, and whose permeability simulation results are in good agreement with the experimental measurements. In addition, the new hybrid method is not only accurate and reliable, but also high efficient and economic, and can be applied to all kinds of reservoir modeling.

Purpose: Preclinical and retrospective studies suggested a role for metformin in sensitizing patients who have diabetes with non–small cell lung cancer (NSCLC) to EGFR tyrosine kinase inhibitors (TKIs). We therefore examined its effects in combination with gefitinib in patients without diabetes harboring EGFR mutations (EGFRm). Patients and Methods: A total of 224 patients without diabetes with treatment-naïve stage IIIB–IV EGFRm NSCLC were randomly assigned in a 1:1 ratio to receive gefitinib plus either metformin or placebo. The primary endpoint was progression-free survival (PFS) rate at 1 year and secondary endpoints included overall survival (OS), PFS, objective response rate (ORR), and safety. Serum levels of IL6 were also examined in an exploratory analysis. Results: The median duration of follow-up was 19.15 months. The estimated 1-year PFS rates were 41.2% [95% confidence interval (CI), 30.0–52.2] with gefitinib plus metformin and 42.9% (95% CI, 32.6–52.7) with gefitinib plus placebo (P = 0.6268). Median PFS (10.3 months vs. 11.4 months) and median OS (22.0 months vs. 27.5 months) were numerically lower in the metformin group, while ORRs were similar between the two arms (66% vs. 66.7%). No significant treatment group differences were detected across all subgroups with respect to PFS, including those with elevated levels of IL6. Metformin combined with gefitinib resulted in a remarkably higher incidence of diarrhea compared with the control arm (78.38% vs. 43.24%). Conclusions: Our study showed that addition of metformin resulted in nonsignificantly worse outcomes and increased toxicity and hence does not support its concurrent use with first-line EGFR-TKI therapy in patients without diabetes with EGFRm NSCLC.

With the rapid development of the economy, various industries are also rapidly growing and progressing, and the machinery manufacturing industry has also made greater breakthroughs. If various industries can achieve the goal of automatic production of machinery, mechanical equipment will be a crucial factor. The machinery manufacturing industry has a lot of room for development, and machinery manufacturing technology has also made tremendous progress. If the machinery and equipment produced by the machinery manufacturing industry become more and more excellent, it needs to try to meet the production needs of all walks of life, and improve the quality of manufacturing equipment. The current problems in the process must be solved, such as equipment failure, safety management.

Background: Travelling to high altitude (HA) presents a risk of the high levels of pulmonary artery pressure (PAP) at altitude, which is associated with impaired exercise capacity and fatal HA pulmonary oedema. However, prediction of high levels of PAP at altitude is still unclear. Methods: Echocardiography and pulmonary function tests were performed on 121 healthy men at low altitude (LA) and 4100 m (5 ± 2 h after a 7 day ascent). Results: HA exposure increased the levels of FEV1/FVC ratio, FEF25%, 50%, 75%, MMEF, mPAP, total pulmonary vascular resistance (PVR) and systolic pulmonary arterial pressure (SPAP). More smokers and lower forced expiratory flow at 25% of forced vital capacity (FEF25%) at LA were observed in subjects with mPAP≥30 mmHg than those with mPAP Conclusions: Thus, these findings suggest that subjects with low FEF25% values at LA are susceptible to high levels of PAP at altitude but not the incidence of AMS following short-term HA exposure, especially in smokers.

Contactin-1 (CNTN-1), a glycosyl phosphatidylinositol anchor neural cell adhesion molecule (ACAM), is thought to function not only in nervous system development but also in the invasion and metastasis of several tumours. To investigate whether CNTN-1 is involved in multidrug resistance (MDR) in lung adenocarcinoma, CNTN-1 expression was compared between MDR human lung adenocarcinoma A549/cisplatin (A549/DDP) cells and its progenitor A549 cells. The comparison showed that CNTN-1 expression in A549/DDP cells was significantly higher than in A549 cells both at the mRNA level and the protein level. In order to confirm the physiological function of the abnormal expression, lentivirus-mediated short hairpin RNA (shRNA) was used to silence CNTN-1. Cell cytotoxicity assay and cell apoptosis assay revealed that silencing CNTN-1 both in A549 cells and in A549/DDP cells not only rendered cells more sensitive to cisplatin than the negative control, but also increased the cisplatin-induced apoptosis. Metastasis and invasion assays demonstrated that CNTN-1 knockdown reduced metastasis and invasion but did not affect A549 or A549/DDP cell proliferation. To investigate whether the abnormal expression of CNTN-1 is associated with characteristics of patients with non-small cell lung cancer (NSCLC), immunohistochemistry was used to detect CNTN-1 expression in 143 tissue samples from NSCLC patients and the results showed that the degree of CNTN-1 expression positively correlated with lymphatic invasion in patients with lung adenocarcinoma who received adjuvant cisplatin- or carboplatin-based treatment after surgery. Thus, we concluded that CNTN-1 is closely related with MDR of lung adenocarcinoma. Additionally, CNTN-1 is a novel marker to predict chemotherapeutic efficacy of patients with lung adenocarcinoma, especially with regard to cisplatin- or carboplatin-based regimens.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated deaths, worldwide, and its prognosis is unfavorable. The aim of this study was to detect serum miR-101 levels in NSCLC patients and investigate its potential diagnostic and prognostic value. A total of 93 patients with NSCLC, 40 cases with various benign lung disease, and 55 healthy volunteers, were enrolled. Quantitative RT-PCR was performed to determine relative serum miR-101 levels in our participants. Decreased serum miR-101 expression was observed in patients with NSCLC and was closely associated with aggressive clinical characteristics. In addition, a significant increase in serum miR-101 levels was found in 36 NSCLC cases after tumor resection. Moreover, receiver-operating characteristic (ROC) curve analysis showed that serum miR-101 was an effective indicator for NSCLC diagnosis. Furthermore, Kaplan-Meier survival curve analysis revealed that low serum miR-101 expression predicted poor overall survival and disease-free survival. Finally, multivariate analysis confirmed serum miR-101 expression was an independent prognostic factor for NSCLC patients. In conclusion, serum miR-101 might serve as a potential biomarker for detection and prognosis evaluation of NSCLC.

The diagnosis of eosinophilic pneumonia (EP) is rare and challenging. This condition is frequently misdiagnosed as pulmonary tuberculosis, lymphoma, schistosomiasis, Wegener's granuloma, severe acute respiratory syndrome, or severe community-acquired pneumonia. Herein, we report a case in which computed tomography (CT)-guided percutaneous lung biopsy was used to diagnose EP without alveolar eosinophilia or peripheral eosinophilia. A roundworm identified in the patient's stool confirmed the precise diagnosis to be parasitic EP. This is, to our knowledge, the first reported case of EP confirmed by CT-guided percutaneous lung biopsy. CT-guided percutaneous lung biopsy may represent a new tool for the diagnosis of EP in patients without typical alveolar eosinophilia or peripheral eosinophilia.

To investigate the predictive value of the acute physiology and chronic health evaluation 2 (APACHE2) score and lung injury prediction score (LIPS) for acute respiratory distress syndrome (ARDS) when combined with biomarkers for this condition in patients with ARDS risk factors. In total, 158 Han Chinese patients with ARDS risk factors were recruited from the Respiratory and Emergency Intensive Care Units. The LIPS, APACHE2 score, primary diagnosis at admission, and ARDS risk factors were determined within 6 h of admission, and PaO2/FiO2 was determined on the day of admission. Blood was collected within 24 h of admission for the measurement of angiopoietin-2 (ANG-2), sE-selectin, interleukin-6 (IL-6), and interleukin-8 (IL-8) levels. ARDS was monitored for the next 7 days. Univariate and multivariate analyses and receiver operating characteristic (ROC) analyses were employed to construct a model for ARDS prediction. Forty-eight patients developed ARDS within 7 days of admission. Plasma ANG-2 level, sE-selectin level, LIPS, and APACHE2 score in ARDS patients were significantly higher than those in non-ARDS patients. ANG-2 level, LIPS, and APACHE2 score were correlated with ARDS (P<0.001, P<0.006, and P<0.042, resp.). When the APACHE2 score was used in combination with the LIPS and ANG-2 level to predict ARDS, the area under the ROC curve (AUC) was not significantly increased. Compared to LIPS or ANG-2 alone, LIPS in combination with ANG-2 had significantly increased positive predictive value (PPV) and AUC for the prediction of ARDS. In conclusion, plasma ANG-2 level, LIPS, and APACHE2 score are correlated with ARDS. Combined LIPS and ANG-2 level displays favorable sensitivity, specificity, and AUC for the prediction of ARDS.

Objectives Early and accurate diagnosis of lung cancer is crucial for effective treatment. This study aimed to identify plasma microRNAs for diagnosis of lung cancer and for further discrimination of small cell lung cancer (SCLC) from non-small cell lung cancer (NSCLC). Materials and methods Plasma microRNA expression was investigated using three independent cohorts including 1132 participants recruited between October 2008 and September 2014 from five medical centers. The subjects were healthy individuals and patients with NSCLC or SCLC. Microarrays were used to screen 723 human microRNAs in 106 plasma samples for candidate selection. Quantitative reverse-transcriptase PCR was applied to evaluate the expression of selected microRNAs. Two logistic regression models were constructed based on a training cohort (n = 565) and then validated using an independent cohort (n = 461). The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. Results Plasma panel A with six microRNAs (miR-17, miR-190b, miR-19a, miR-19b, miR-26b, and miR-375) provided high diagnostic accuracy in discriminating lung cancer patients from healthy individuals (AUC 0.873 and 0.868 for training and validation cohort, respectively). Moreover, plasma panel B with three microRNAs (miR-17, miR-190b, and miR-375) demonstrated high diagnostic accuracy in discriminating SCLC from NSCLC (AUC 0.878 and 0.869 for training and validation cohort, respectively). Conclusion We constructed and validated two plasma microRNA panels that have considerable clinical value in diagnosis of lung cancer, and could play an important role in determining optimal treatment strategies based on discrimination between SCLC and NSCLC.

Background: Anlotinib (AL3818) is a novel multitarget tyrosine kinase inhibitor, inhibiting tumour angiogenesis and proliferative signalling. The objective of this study was to assess the safety and efficacy of third-line anlotinib for patients with refractory advanced non-small-cell lung cancer (RA-NSCLC). Methods: Eligible patients were randomised 1 : 1 to receive anlotinib (12 mg per day, per os; days 1–14; 21 days per cycle) or a placebo. The primary end point was progression-free survival (PFS). Results: A total of 117 eligible patients enrolled from 13 clinical centres in China were analysed in the full analysis set. No patients received immune check-point inhibitors and epidermal growth factor receptor status was unknown in 60.7% of the population. PFS was better with anlotinib compared with the placebo (4.8 vs 1.2 months; hazard ratio (HR)=0.32; 95% confidence interval (CI), 0.20–0.51; P

With the rapid development of knowledge information and internet technology, a variety of online knowledge paid products and knowledge payment platforms are widely used by college students. The satisfaction evaluation of knowledge payment platform not only helps college students choose a suitable knowledge payment platform, but also helps the knowledge payment platform improve competitiveness and standardization. This paper collects customer satisfaction data by designing questionnaires and conducting customer satisfaction surveys. Using statistical analysis methods such as descriptive statistics, parameter testing and reliability analysis, the customer satisfaction data are analyzed from different dimensions. Based on American customer satisfaction index (ACSI) and the characteristics of knowledge payment, content quality, technical quality, update frequency and advertising marketing quality are extracted as important factors for satisfaction evaluation. Then, a satisfaction evaluation model of knowledge payment platform is constructed to evaluate the satisfaction degree of college students on the knowledge payment platform by employing factor analysis and multivariable regression analysis. The proposed model can predict the development trend of knowledge payment platforms and provide valuable suggestions for the healthy development and the selection of knowledge payment platforms.

9035 Background: Several lines of evidence suggested a role for metformin in sensitizing diabetic NSCLC patients to EGFR tyrosine kinase inhibitors (TKIs). However, data regarding its effects on non-diabetic populations remained scarce. We hereby examined metformin’s first-line use alongside gefitinib in EGFR mutation positive (EGFRm) patients without diabetes. Methods: In this trial (NCT01864681), 224 non-diabetic patients with treatment naïve stage IIIB-IV EGFRm NSCLC were randomly assigned at 1:1 to receive gefitinib plus metformin or placebo. Gefitinib was administered at 250 mg once daily, while metformin/placebo was initiated at 500 mg once daily and then escalated to 1000 mg twice daily over 2 weeks. Dose reduction was permitted for metformin/placebo in case of intolerable toxicity. The primary endpoint was progression-free survival (PFS) rate at 1 year. Secondary endpoints were overall survival (OS), PFS, objective response rate (ORR), and safety. Serum levels of interleukin-6 were also subjected to exploratory analysis. Results: Baseline characteristics were well balanced between treatment groups. The median duration of follow-up was 19.15 (IQR 12.99-28.44) months. The estimated 1-year PFS rate was 41.2% (95% confidence interval [CI] 30.0-52.2) in the metformin group versus 42.9% (95% CI 32.6-52.7) in the placebo group (p = 0.6268). Metformin did not increase median PFS (10.3 months vs. 11.4 months), median OS (22.0 months vs. 27.5 months), or ORR (66.0% vs. 66.7%) over placebo. No significant treatment group differences in terms of PFS were detected across subgroups either, including those with elevated levels of interleukin-6. Metformin plus gefitinib shared a similar safety profile with the control group, except for a remarkably higher incidence of diarrhea (78.38% vs. 43.24%). Conclusions: Our study did not show enhanced gefitinib efficacy upon addition of metformin and hence does not support its concurrent use with first-line EGFR-TKI therapy in non-diabetic EGFRm NSCLC patients. Clinical trial information: NCT01864681.

Although aberrant DNA methylation has been implicated in the pathophysiology of lung cancer, the role of methylation in multidrug resistance (MDR) of lung cancer has remained unclear. To investigate whether certain distinct DNA methylation pattern is associated with acquired MDR of lung adenocarcinoma, methylated-DNA immunoprecipitation-chromatin immunoprecipitation (MeDIP-ChIP) was utilised to compare the genome-wide promoter methylation of the human lung adenocarcinoma MDR A549/cisplatin (A549/DDP) cells with its progenitor A549 cells. The comparison identified 3617 genes with differentially methylated promoter, of which 1581 were hypermethylated and 2036 were hypomethylated. Then, bisulphite sequencing polymerase chain reaction (PCR) (BSP) and quantitative reverse transcription (RT)-PCR (Q-PCR) were used to validate the promoter methylation of five candidate genes and to determine whether the expression of genes was associated with the promoter methylation. BSP confirmed that the promoter methylation incidence of the hypermethylated genes, G protein-coupled receptor 56 isoform 3 (GPR56), metallothionein 1G (MT1G), and RAS association domain family gene 1 (RASSF1), was significantly higher in A549/DDP cells compared with A549 cells (p

The interplay of a complex genetic basis with the environmental factors of chronic obstructive pulmonary disease (COPD) may account for the differences in individual susceptibility to COPD. Mitochondrial DNA (mtDNA) contributes to an individual's ability to resist oxidation, an important determinant that affects COPD susceptibility. To investigate whether mtDNA haplogroups play important roles in COPD susceptibility, the frequencies of mtDNA haplogroups and an 822-bp mtDNA deletion in 671 COPD patients and 724 control individuals from southwestern China were compared. Multivariate logistic regression analysis revealed that, whereas mtDNA haplogroups A and M7 might be associated with an increased risk for COPD (OR=1.996, 95% CI=1.149-2.831, p=0.006, and OR=1.754, 95% CI=1.931-2.552, p=0.021, respectively), haplogroups F, D, and M9 might be associated with a decreased risk for COPD in this population (OR=0.554, 95% CI=0.390-0.787, p=0.001; OR=0.758, 95% CI=0.407-0.965, p=0.002; and OR=0.186, 95% CI=0.039-0.881, p=0.034, respectively). Additionally, the increased frequency of the 822-bp mtDNA deletion in male cigarette-smoking subjects among COPD patients and controls of haplogroup D indicated that haplogroup D might increase an individual's susceptibility to DNA damage from external reactive oxygen species derived from heavy cigarette smoking. We conclude that haplogroups A and M7 might be risk factors for COPD, whereas haplogroups D, F, and M9 might decrease the COPD risk in this Han Chinese population.

Background: Biapenem is an injectable carbapenem antibiotic. A clinical study was designed to evaluate its efficacy and safety in the treatment of respiratory and urinary infections compared to imipenem/cilastatin. Methods: A total of 216 patients with respiratory or urinary tract infections were enrolled into this multicenter, open-label, randomized controlled clinical study. Each patient was randomly assigned to either the treatment or control group; 106 patients in each group were included in the ITT analyses. The patients were given biapenem 300 mg or imipenem/cilastatin 500 mg/500 mg two or three times daily, i.v. g.t.t. for 7–14 days according to their conditions. Results: The cure and effective rates were 67.92 and 88.68% in the biapenem group and 76.02 and 93.40% in the imipenem/cilastatin group, the bacterial eradication rates were 93.83 and 98.82%, and the adverse-event rates were 6.54 and 7.41%, respectively. There were no significant differences between the two groups (p > 0.05). Conclusion: Biapenem is as effective and well-tolerated as imipenem/cilastatin for the treatment of intermediate and severe bacterial infections.

// Chaowen Jiang 1, * , Shilong Yu 1, * , Pin Qian 1, * , Ruiling Guo 2 , Ruijie Zhang 3 , Zhi Ao 1 , Qi Li 1 , Guoming Wu 1 , Yan Chen 1 , Jin Li 1 , Changzheng Wang 1 , Wei Yao 1 , Jiancheng Xu 1 , Guisheng Qian 1 , Fuyun Ji 1 1 Institute of Human Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China 2 Department of Respiratory Diseases, 324 th Hospital of People’s Liberation Army (No.324 Hospital of PLA), Chongqing 400020, China 3 Department of Respiratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China * These authors have contributed equally to this work Correspondence to: Fuyun Ji, email: JiF@email.chop.edu , jifuyun@263.net Guisheng Qian, email: qiangs1220@163.com Keywords: lung cancer, risk, TOX3/LOC643714, polymorphisms, breast cancer Received: February 02, 2016 Accepted: July 09, 2016 Published: July 28, 2016 ABSTRACT It has been well established that besides environmental factors, genetic factors are also associated with lung cancer risk. However, to date, the prior identified genetic variants and loci only explain a small fraction of the familial risk of lung cancer. Hence it is vital to investigate the remaining missing heritability to understand the development and process of lung cancer. In the study, to test our hypothesis that the previously identified breast cancer risk-associated genetic polymorphisms at the TOX3/LOC643714 locus might contribute to lung cancer risk, 16 SNPs at the TOX3/LOC643714 locus were evaluated in a Han Chinese population based on a case-control study. Pearson’s chi-square test or Fisher’s exact test revealed that rs9933638, rs12443621, and rs3104746 were significantly associated with lung cancer risk ( P < 0.001, P < 0.001, and P = 0.005, respectively). Logistic regression analyses displayed that lung cancer risk of individuals with rs9933638(GG+GA) were 1.89 times higher than that of rs9933638AA carriers (OR = 1.893, 95% CI = 1.308-2.741, P = 0.001). Similar findings were manifested for rs12443621 (OR = 1.824, 95% CI = 1.272-2.616, P = 0.001, rs12443621(GG+GA) carriers vs. rs12443621AA carriers) and rs3104746 (OR = 1.665, 95% CI = 1.243-2.230, P = 0.001, rs3104746TT carriers vs. rs3104746(TA+AA) carriers). The study discovered for the first time that three SNPs (rs9933638, rs12443621, and rs3104746) at the TOX3/LOC643714 locus contributed to lung cancer risk, providing new evidences that lung cancer and breast cancer are linked at the molecular and genetic level to a certain extent.

By simulating real working conditions of household photovoltaic system, the effects of overcharging on lifetime of valve-regulated lead-acid (VRLA) battery in solar home systems have been investigated; and the influences of three kinds of charge regulator strategies on state of charge and lifetime of VRLA battery have also been studied by experiments. A quantitative analysis of the VRLA battery behaviour under different charge regulator strategies was carried out. It is found that the temperature compensation of the end-of-charge voltage is necessary for VRLA battery, particularly in hot climates. The linear temperature compensation for the end-of-charge voltage keeps VRLA battery the best state of charge compared with other charge regulator strategies. Based on our results, the design engineers can choose a cost-effective regulator according to the details of photovoltaic system and local climate, and can estimate working state of VRLA battery installed in a system correctly, so as to extend VRLA battery lifetime in solar home systems. The clarification of the performance difference of VRLA battery under different regulators may be an important issue for determining life-cycle costs and servicing requirements.

This paper describes some strategies for meeting challenges to the grid's ability to provide reliable power delivery. The goal is to provide a vision for a comprehensive and systematic approach to meet the criteria for grid safety and reliability through new information services.

To explore the efficacies and toxicities of different platinum-based combination chemotherapeutic regiments for patients with advanced non-small cell lung cancer (NSCLC).A total of 239 advanced NSCLC from January 2011 to December 2012 were reviewed in Xinqiao Hospital. The chemotherapeutic efficacies and adverse effects in the first-line treatment of advanced NSCLC by paclitaxel plus platinum (paclitaxel group, n = 113), gemcitabine plus platinum (gemcitabine group, n = 72) and docetaxel plus platinum (docetaxel group, n = 54) regiments were retrospectively analyzed and compared. Their efficacies and toxicities were analyzed by Chi-square test. And survival was estimated with Kaplan-Meier method.The objective response rate (ORR) of three groups were 42.5%, 43.1% and 35.2% respectively (P = 0.612). The disease control rate (DCR) were 84.1%, 75.0% and 74.1% respectively (P = 0.198). The median progression-free survival was 5.6, 5.8 and 3.2 months respectively (P = 0.000). The major adverse effects were myelosuppression, gastrointestinal reaction, alopecia and neurotoxicity, etc. The incidence rate of neurotoxicity among three groups were 34.5% (39/113), 11.1% (8/72) and 18.5% (10/54) respectively (P = 0.001).No significant inter-group difference of adverse effects existed (all P0.05), except for neurotoxicity.Three platinum-based combination chemotherapeutic regiments produce excellent efficacies with acceptable adverse effects. Their ORR and DCR were similar. And the median progression-free survival of paclitaxel and gemcitabine groups is significantly longer than that of docetaxel group.

BackgroundLPS-binding protein (LBP) and its ligand CD14 are located upstream of the signaling pathway for LPS-induced inflammation. Blocking LBP and CD14 binding might prevent LPS-induced inflammation. In previous studies, we obtained a peptide analog (MP12) for the LBP/CD14 binding site and showed that this peptide analog had anti-endotoxin activity. In this study, we used in vitro directed evolution for this peptide analog to improve its in vivo and in vitro anti-endotoxin activity.MethodsWe used error-prone PCR (ep-PCR) and induced mutations in the C-terminus of LBP and attached the PCR products to T7 phages to establish a mutant phage display library. The positive clones that competed with LBP for CD14 binding was obtained by screening. We used both in vivo and in vitro experiments to compare the anti-endotoxin activities of a polypeptide designated P1 contained in a positive clone and MP12.Results11 positive clones were obtained from among target phages. Sequencing showed that 9 positive clones had a threonine (T) to methionine (M) mutation in amino acid 287 of LBP. Compared to polypeptide MP12, polypeptide P1 significantly inhibited LPS-induced TNF-α expression and NF-κB activity in U937 cells (PConclusionBy in vitro directed evolution of peptide analogs for the LBP/CD14 binding site, we established a new polypeptide (P1) with a threonine (T)-to-methionine (M) mutation in amino acid 287 of LBP. This polypeptide had high anti-endotoxin activity in vitro and in vivo, which suggested that amino acid 287 in the C-terminus of LBP may play an important role in LBP binding with CD14.

The single path model of airway gas transport, with and without a distributed blood source term, was used to simulate multiple-breath N2 washout by breathing pure O2 in two lung models: a single-region lung model (SRLM) which produces series inhomogeneity, and a seven-region lung model (7RLM) incorporating both series and parallel inhomogeneities. Normalized phase III slopes (Sn) from N2 expirograms were computed for each breath and compared with published human experimental data obtained under similar conditions. The 7RLM predicts well the trend of experimental Sn N2 changes and is superior to the SRLM in the first part (the unsteady state), implying that this part of the curve is mostly due to convective mixing of the seven parallel flow streams. In the quasi-steady state, the 7RLM is not obviously superior to the SRLM. Functional residual capacity and pulmonary perfusion are shown to strongly affect the number of breaths required to reach the quasi-steady state. The anatomical dimensions that appear to be critical in SRLM are not as important in the 7RLM.

Mitochondrial DNA (mtDNA) is particularly susceptible to oxidative damage and mutation due to the high rate of reactive oxygen species (ROS) production and limited DNA-repair capacity in mitochondrial. Previous studies demonstrated that the increased mtDNA copy number for compensation for damage, which was associated with cigarette smoking, has been found to be associated with lung cancer risk among heavy smokers. Given that the common and "non-pathological" mtDNA variations determine differences in oxidative phosphorylation performance and ROS production, an important determinant of lung cancer risk, we hypothesize that the mtDNA variations may play roles in lung cancer risk. To test this hypothesis, we conducted a case-control study to compare the frequencies of mtDNA haplogroups and an 822 bp mtDNA deletion between 422 lung cancer patients and 504 controls. Multivariate logistic regression analysis revealed that haplogroups D and F were related to individual lung cancer resistance (OR = 0.465, 95%CI = 0.329-0.656, p

Background: Prulifloxacin is a promising fluoroquinolone antibiotic. A multicentre, double-blind, randomized clinical study was designed to evaluate its efficacy and safety compared to that of levofloxacin for the treatment of respiratory and urinary infections of Chinese patients. Methods: A total of 267 patients were enrolled and each was randomly assigned to either the treatment or the control group. Prulifloxacin 264.2 mg (equivalent to ulifloxacin 200 mg) b.i.d. or levofloxacin hydrochloride 200 mg b.i.d. was administered orally for 5–14 days according to a patient’s condition. The clinical response, bacterial eradication and incidence of adverse events were evaluated. Results: Two hundred and forty-three patients completed the study. For the modified intention-to-treat population, the cure and effective rates were 45.53 and 82.93% in the prulifloxacin group and 49.18 and 83.61% in the levofloxacin group. For the per-protocol analysis population, the cure and effective rates were 45.90 and 83.61% in the prulifloxacin group and 49.59 and 83.47% in the levofloxacin group. The bacterial eradication rates were 96.59 and 95.35%, and the drug-related adverse event rates were 7.87 and 5.51% in the prulifloxacin and levofloxacin group, respectively. The cure rate and efficacy rate of respiratory and urinary tract infections of the levofloxacin group were better than those of the prulifloxacin group. However, the difference between the 2 groups was not statistically significant (p > 0.05). Conclusion: Prulifloxacin is as effective and well tolerated as levofloxacin in the treatment of respiratory and urinary tract infections.