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Compared with other lung squamous cell carcinomas (LUSC), pulmonary lymphoepithelioma-like carcinoma (pLELC) is closely associated with Epstein–Barr virus infections with a unique molecular profile and immune microenvironment. The purpose of this study was therefore to compare the treatment response and effectiveness of immunotherapy between pLELC and LUSC. We enrolled 31 patients with pLELC and 116 with LUSC receiving first-line immunotherapy at three centers in China and compared the treatment response and effectiveness of immunotherapy. Propensity score matching (PSM) was used to balance the differences in baseline data between the two groups. Before PSM, progression free survival and overall survival was longer in the pLELC group than that of the LUSC group (Progression free survival: HR, 1.67; 95% CI: 1.05–2.63, P=0.028. Overall survival: HR, 1.9; 95% CI: 1.06–3.4, P=0.028). This remained unchanged after PSM (Progression free survival: HR,1.79; 95% CI: 1.02–3.15, P=0.044. Overall survival: HR,2.2; 95% CI: 1.1–4.37, P=0.022). In conclusion, pLELC showed a clinically meaningful survival benefit compared with traditional LUSC following immunotherapy. Subsequent studies should consider the role of the Epstein–Barr virus in the tumor immune microenvironment of pLELC.

Facing the increase of consumer heterogeneous demand, green manufacturers and retailers need to get accurate and timely consumer preference information to better meet the consumer demand. In the big data era, a massive amount of demand data can be collected by advanced technologies, which can help manufacturers and retailers predict consumer preferences more accurately. However, big data technology also brings additional information cost to low-carbon supply chains. Therefore, it is necessary to rethink the pricing and carbon emission reduction decisions in the new situations. The purpose of this paper is to explore the influence of big data technology on pricing and carbon emission reduction decisions in low-carbon supply chain considering the retailers’ fairness concerns. By constructing Stackelberg game models, the optimal pricing and carbon emission reduction decisions are presented. Results indicate that the use of big data technology can increase both the profit of manufacturer and the utility of retailer, and can promote manufacturer to improve the carbon emission reduction level.

The optimization of cutter shape has become one of the main innovation direction of PDC bit technology. At present, both domestic and foreign bit manufacturers have put forward various special shaped cutters to improve rock breaking efficiency. However, there are relatively few researches which focus on the rock breaking efficiency of special-shaped cutters. Therefore, three kinds of typical cutters (flat cutter, convex cutter and concave cutter) are selected as the study object in this paper. Based on the single cutter test, the relationship of axial cutting force, cutting area and cutting specific energy under different working conditions will be provided. The experimental results show that the axial cutting force and specific energy of concave cutter and convex cutter are lower than that of flat cutter in most test cases. The results are almost the same for both Vosges sandstone and Marcellus shale cases. In other words, the tested concave cutters are easier to intrude into rock and obtain higher rock brea king efficiency under the same cutting conditions, when compared with flat cutter and convex cutter. The experimental method provides a technica l reference for studying the rock breaking efficiency of three-dimensional cutters with different shapes.

Clazosentan therapy has been found to be effective in reducing the incidence of vasospasm after aneurismal subarachnoid hemorrhage (aSAH). The objective of this meta-analysis was to determine whether different doses of clazosentan treatment significantly reduced the incidence of delayed ischemic neurological deficits (DINDs) and new cerebral infarction (NCI). We systematically searched PubMed, Embase, Cochrane library and Medline from inception until October, 2015. All randomized controlled trials related to the functions of clazosentan in aSAH were included. Analyses were performed following the method guideline of Cochrane Back Review Group. Four randomized placebo-controlled trials met eligibility criteria and enrolled a total of 2159 patients. The meta-analysis demonstrated a significant decrease in the incidence of DINDs (relative risk, 0.49 and 95% CI, 0.33-0.73) and NCI (relative risk, 0.42 and 95% CI, 0.25-0.71) in patients treated with a high dose of clazosentan (15 mg/h) after aSAH. In addition, a high dose of clazosentan (15 mg/h) had no more effect on the incidence of adverse events than that of a low dose (1-5 mg/h). The results of the present meta-analysis show that a high dose of clazosentan significantly reduced the incidence of the vasospasm-related DINDs and NCI. Further study is required to fully understand the potential usefulness of clazosentan in patients with aSAH.

BACKGROUND: The aim of this research was to evaluate the effect of spatial location of tumors on the prognosis of patients with left upper lung non-small cell lung cancer (NSCLC), with a focus on the S1+2+3 and lingual segment. METHODS: A total of 486 patients who underwent lobectomy and systematic lymph node dissection were collected retrospectively in this study (354 S1+2+3 and 132 lingual segment patients). Factors impacting survival were assessed via univariate analyses, multivariate analyses, and log-rank tests. RESULTS: Compared with tumor location in S1+2+3, lingual segment tumor location of stage II to III left upper lung NSCLC patients was significantly associated with a better 5-year disease-free survival (DFS) (P=0.041). Multivariate analysis results showed that tumor location in the lingual segment was a good independent prognostic factor of stage II to III left upper lung NSCLC patients [hazard ratio (HR) =0.602, 95% confidence interval (CI): 0.149–0.865, P=0.006). However, in stage I left upper lung NSCLC, tumor location (HR =1.069, 95% CI: 0.571–2.000, P=0.835) was not an independent prognostic factor, and only T2 (HR =2.422, 95% CI: 1.271–4.620, P=0.007) was an independent worse prognosis factor. CONCLUSIONS: Tumor location in the lingual segment of left upper lung stage II to stage III NSCLC is a good independent prognostic factor compared with S1+2+3. Nevertheless, tumor location does not impact the prognosis of patients with stage I NSCLC in the left upper lung.

Vandetanib, a tyrosine kinase inhibitor used as an anticancer therapeutic agent, has adverse events associated with treatment resulting in noncompliance and withdrawal from the therapy. Here, we performed meta-analysis of published clinical trials to determine relative risk (RR) and incidence of gastrointestinal events during vandetanib therapy in patients with cancer. A comprehensive literature search was performed and summary incidence, RR, and 95% confidence intervals (CIs) were calculated employing fixed- or random-effects models, depending on the heterogeneity of trials. Twenty-two trials with 6382 patients were included summary incidences of all-grade gastrointestinal events in patients with cancer were anorexia 24% (95% CI, 20%-28%), constipation 17% (95% CI, 13%-20%), diarrhea 46% (95% CI, 40%-53%), nausea 29% (95% CI, 25%-33%), and vomiting 17% (95% CI, 14%-21%). Incidences of vandetanib-associated gastrointestinal events stratified by tumor histology were statistically insignificant. Vandetanib was associated with a significant risk of all-grade diarrhea (RR 1.75, 95% CI, 1.42-2.16) and high-grade diarrhea (RR 1.94, 95% CI, 1.43-2.64) and significantly decreased risk of all-grade constipation (RR 0.80, 95% CI, 0.71-0.91). Summary RR showed a significant risk of vandetanib-associated constipation (RR 0.82, 95% CI, 0.72-0.93) and diarrhea (all-grade: RR 1.68, 95% CI, 1.31-2.14 and high-grade: RR 1.57, 95% CI, 1.14-2.17) in patients with non-small-cell lung cancer. This study revealed a significantly increased risk of diarrhea and a reduced risk of constipation in patients with cancer receiving vandetanib, suggesting that appropriate and frequent clinical monitoring should be emphasized.

Background Sorafenib is a relatively new multi-kinase inhibitor used to treat a wide range of cancers. As fatal adverse events from sorafenib therapy are rare, their investigation requires a meta-analysis. Aim of the review To provide a meta-analysis of sorafenib-associated fatal adverse events with the most expansive and current data. Method We searched Medline, EMBASE, Web of Science and Cochrane Library databases. We also searched abstracts from a number of conferences. Twenty trials of sorafenib were found in 9434 cancer patients, tested against placebos and against other drugs. We calculated relative risks and incidences for sorafenib-associated mortality. Results Overall incidence of sorafenib-associated mortality was 3.3 %. Patients with renal cell carcinoma (RCC) and thyroid cancer had treatment-related mortality ≥5 %. Patients treated with sorafenib had a significantly greater risk of mortality than those in placebo/control groups, with an RR of 1.75. Subgroup analyses also showed significant differences in sorafenib versus placebo (RR 1.87, 95 % CI 1.23–2.86; I 2 = 0.0 %, P = 0.865); and sorafenib + platinum-based chemotherapy (RR 2.03, 95 % CI 1.15–3.59; I 2 = 0.0 %, P = 0.654). However, sorafenib had lower risk than other multi-targeted antiangiogenic tyrosine kinase inhibitors. Patients with RCC and non-small-cell lung carcinoma were significantly more vulnerable. Conclusion Sorafenib presents a significant risk of fatal adverse events (FAEs) in patients with cancer, especially for RCC or non-small-cell lung carcinoma, and in patients treated with sorafenib + platinum-based chemotherapy. However, compared with other multi-targeted antiangiogenic tyrosine kinase inhibitors, sorafenib has a lower risk of FAEs.

For the ultra-deep ultra-high pressure wells in the Kuqa foreland basin of the Tarim basin in western China, it has been an ongoing challenge for more than a decade to drill through the Cretaceous Bashijiqike (K1bs) formation in a more efficient and economical manner. It is comprised of sandstone and mudstone with abundant natural fractures in the upper K1bs with frequent severe fluid loss occurrence and middle and bottom K1bs are both comprised of highly compacted sandstone, mudstone and siltstone without the presence of natural fractures. In the past, it requires an average of 8, and sometimes up to 16, premium PDC bits and more than 90 days to complete the target interval. This paper discusses the continuous effort in the development and introduction of ongoing bit technologies to drill through the Bashijiqike Formation and the development of methodology that tailors different bit technologies to different sections of the Bashijiqike formation according to drillability characteristics. Dissecting the formation into different sub-zones and matching them with suitable bit technologies results desirable efficiency and significant cost reduction.

Lapatinib, a tyrosine kinase inhibitor used as an anticancer therapeutic agent, has adverse events associated with treatment resulting in noncompliance and withdrawal from the therapy. Here, we performed meta-analysis of published clinical trials to determine relative risk (RR) and incidence of gastrointestinal events during lapatinib therapy in patients with cancer. A comprehensive literature search was performed and summary incidence, RR, and 95% confidence intervals (CI) were calculated using fixed-effects or random-effects models, depending on the heterogeneity of trials. Thirty-six trials with 12,402 patients were included; summary incidences of all-grade gastrointestinal events in patients with cancer were diarrhea 57.8%, nausea 30.8%, and vomiting 19.6%. Lapatinib combination with chemotherapy or any anti-HER2 mAbs were associated with significant risk of all-grade diarrhea [(RR 3.64, 95% CI, 2.96-4.49), (RR 2.89, 95% CI, 2.21-3.79), respectively] and high-grade diarrhea [(RR 11.25, 95% CI, 7.31-17.33), (RR 9.96, 95% CI, 7.23-13.72), respectively], and lapatinib combination with chemotherapy group showed a significantly increased risk of all-grade nausea (RR 1.54, 95% CI, 1.25-1.89). Lapatinib combination with chemotherapy or any anti-HER2 mAbs were associated with significant risk of all-grade vomiting [(RR 1.47, 95% CI, 1.12-1.93), (RR 1.30, 95% CI, 1.11-1.52), respectively]. Lapatinib combination with any anti-HER2 mAbs was associated with a significant risk of high-grade vomiting (RR 2.25, 95% CI, 1.41-3.61). This study revealed a significantly increased risk of diarrhea, nausea, and vomiting in patients with cancer receiving lapatinib, suggesting that appropriate clinical intervention and gastrointestianal protective agents should be emphasized.

This paper provides tensile testing and analysis at the hybrid fiber model composites mechanical process measuring. In this study, tensile tested of hybrid fiber composites was accomplished using a mechanical high-efficiency propeller technology. This research result suggests that the tensile testing of hybrid fiber composites acquired for horizontal direction length is a eliminated gravity influence factors measurement as a representative strength. The mechanical technique is validated by comparison with results from a similar tensile tested using several groups specimens. Surprisingly, double-fixtures only severe affects the results.

Sorafenib is a new multikinase inhibitor; the incidence of hypertension (HTN) with sorafenib has been reported to vary substantially among clinical trials. We searched multiple databases to investigate the risk of sorafenib-induced HTN in patients with cancer. A total of 93 trials involving 20,494 patients were selected for this meta-analysis. The relative risks (RRs) of all-grade and high-grade HTN associated with sorafenib were 3.06 (P < 0.001) and 3.33 (P < 0.001). There are no significantly RRs of all-grade, 0.81 (P = 0.047), and high-grade HTN, 0.64 (P = 0.075), in sorafenib monotherapy versus other multitargeted antiangiogenic tyrosine kinase inhibitors. The incidence of sorafenib-associated all-grade and high-grade HTN was 21.3% (P < 0.001) and 5.9% (P < 0.001), respectively. The patients with renal cell carcinoma (RCC) and thyroid cancer have high incidence (≥20%) of sorafenib-associated all-grade HTN and high incidence (≥5%) of sorafenib-associated high-grade HTN. The trials with median treatment duration ≥ 4, 5, and 7 months were 21.0% (P < 0.001), 25.4% (P < 0.001), and 27.6% (P < 0.001); progression-free survival ≥ 6, 9, and 12 months were 24.5% (P < 0.001), 26.8% (P < 0.001), and 32.8% (P < 0.001); and overall survival ≥ 12, 18, and 24 months were 18.5% (P < 0.001), 22.5% (P < 0.001), and 25.9% (P < 0.001), respectively. There is a significantly high risk of sorafenib-induced HTN. In comparison between sorafenib and other multitargeted antiangiogenic tyrosine kinase inhibitors, RRs had no significance. The patients with RCC and thyroid cancer have significantly higher incidence of HTN. With prolonged treatment duration, progression-free survival, and overall survival, the incidence of all-grade HTN may increase.

Altered expression of paxillin (PXN) is closely linked to the pathogenesis progression, metastasis and prognosis of different malignancies including gastric cancer (GC). Epigenetic silencing of tumor-suppressive microRNAs (miRNAs) is a crucial component of the mechanism underlying activation of oncogenes in tumor. To screen for epigenetically silenced miRNAs which target PXN in GC, we performed bioinformatics algorithms and real-time PCR analysis, and identified miR-212 as the optimum candidate gene. A luciferase reporter gene assay validated that miR-212 directly targets the 3’UTR region of PXN. Importantly, miR-212 levels were inversely correlated with PXN expression in GC cell lines and clinical tumor tissues. The use of miR-212 minics decrease PXN mRNA and protein level in GC cell lines. Moreover, low expression of miR-212 and its promoter hypermethylation were causally related and were associated with aggressive tumor phenotype and adverse prognosis in GC. Restoring mir-212 expression by exogenous mirprecursor molecules transfection or reexpression of endogenous miR-212 treated by 5-aza-2’-deoxycytidine (5-aza) can exert similar effect that reduce GC cells invasion and metastasis abilities in vitro by interacting PXN gene. In addition, 5-aza-induced PXN reduction could be partically blocked by miR-212 inhibitor, resulting in a reversal of weankening cell migration and invasion ability of 5-aza. A rescue experiment and a loss-of-function experiment in vitro and vivo showed that PXN restoration rescues migration and invasion phenotype in miR-212 overexpressed GC cell lines and PXN knockdown blocks GC cells migration and invasion in the presence miR-212 inhibitors. Taken together, our results clearly show that overexpression of PXN induced by methylationsuppressed miR-212 promotes tumor metastasis and invasion, and regulation of miR-212 expression may be a novel therapeutic strategy for gastric cancer.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been extensively investigated in previously treated advanced non-small-cell lung cancer (NSCLC), but what it is still unclear is the efficacy of (EFGR-TKIs: gefitinib or erlotinib) monotherapy in previously treated non-small-cell lung cancer (NSCLC). In December 2013, we performed a search in the PubMed, EMBASE, Cochrane library databases and Web of Science for randomized trials exploring the role of gefitinib or erlotinib in advanced non-small cell lung cancer. Through strict inclusion and exclusion criteria, fourteen trials (three front-line, two second-line, nine maintenance, n = 8970 patients) were eligible. EGFR-TKIs significantly increased overall survival (OS) [hazard ratio (HR) 0.88, 95 %confidence interval (CI) 0.82–0.96, I2 = 50.5 %] and progression-free survival (PFS) (HR 0.71, 95 % CI 0.63–0.81, I2 = 81.2 %] compared with placebo or best support care (BSC). Patients with clinical features such as never smoker, adenocarcinoma, Asian ethnicity and EGFR mutation positive had more pronounced OS and PFS benefit. The main adverse reactions were diarrhea, rashes, anorexia and anemia, [odds ratio (OR) = 3.635, 95 % confidence interval (CI) = (2.377 to 5.557)], [OR = 15.664, 95 %CI = (8.869 to 27.665)], [OR = 1.555, 95 %CI = (1.060 to 2.283)], [OR = 1.481, 95 %CI = (1.114 to 1.969)], respectively. The results show that monotherapy therapy with EFGR-TKIs produce a significant OS and PFS benefit for patients with NSCLC compared with placebo or BSC, especially for the patients who had adenocarcinomas, non-smokers and patients with EGFR gene mutations.

Mechanism that is designed and assembled digitally and lately manufactured directly without post-assembly is called non-assembly mechanism. Selective Laser Melting (SLM) is a desirable technology for manufacturing non-assembly mechanisms directly as it can make complex functional parts directly. The critical factors of manufacturing non-assembly mechanisms by SLM such as display strategy and dimensional accuracy of clearance character are investigated in this paper. Non-assembly mechanisms such as Copper Cash Abacus and Collapsible Abacus, planar linkages (slider-crank, crank-rocker, rocker-slider) and universal joint, etc are freely designed and are manufactured by DiMetal-100 series SLM equipment. It is shown that SLM can not only manufacture parts with complex structures successfully, but also can manufacture non-assembly mechanisms with motion performance directly. It provides a feasible method for the digital design and integrated fabrication of mechanical and electronic products. Published version

The LED lighting applied to rolling stock adequately based on the operating environ,ment and the characteristic of LEDs is developed. The LED driving circuit, heat sink, and mechanical structure are discussed in the paper, and the simulation to the LED matrix circuit with ANSYS is used to analyze the heat dissipation. The experiment provided the evidence that the train onboard LED lamp designed is adequate for electromagnet and vibration environment of a running train.