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ObjectiveThis study aimed to detect circulating tumor cells (CTCs) and circulating tumor-derived endothelial cells (CTECs) in patients with advanced lung cancer, for describing the distribution characteristics of CTC and CTEC subtypes, exploring the correlation between CTC/CTEC subtypes and novel prognostic biomarkers.MethodsA total of 52 patients with advanced lung cancer were enrolled in this study. Using the subtraction enrichment-immunofluorescence in situ hybridization (SE-iFISH) system, CTCs and CTECs derived from these patients were identified.ResultsBased on cell size, there were 49.3% small and 50.7% large CTCs, and 23.0% small and 77.0% large CTECs. Triploidy, tetraploidy, and multiploidy varied in the small and large CTCs/CTECs. Besides these three aneuploid subtypes, monoploidy was found in the small and large CTECs. Triploid and multiploid small CTCs and tetraploid large CTCs were associated with shorter overall survival (OS) in patients with advanced lung cancer. However, none of the CTECs subtypes showed a significant correlation with patient prognosis. In addition, we found strong positive correlations (Pmultiploid small cell size CTECs, and multiploid small cell size CTCs and monoploid small cell size CTECs. Furthermore, combined detection of the specific subtypes, including triploid small CTC and monoploid small CTEC, triploid small CTC and triploid small CTEC, and multiploid small CTC and monoploid small CTEC, were associated with poor prognosis in advanced lung cancer.ConclusionsAneuploid small CTCs are associated with the outcome of patients with advanced lung cancer. In particular, the combined detection of triploid small CTCs and monoploid small CTECs, triploid small CTCs and triploid small CTECs, and multiploid small CTCs and monoploid small CTECs has clinical significance for predicting prognosis in patients with advanced lung cancer.

BACKGROUND: Anaplastic lymphoma kinase (ALK) gene rearrangement is a series of mutations of non-small cell lung cancer (NSCLC) patients. Since 2011, multiple ALK inhibitors (ALKis) have been developed and launched for targeted therapy. In this study, we sought to investigate different strategies of sequential applying the ALKis and their clinical benefits to the overall survival (OS). METHODS: A total of 176 patients with advanced NSCLC (stage IIIB–IV) harboring the ALK rearrangement were included in this cohort study. They were diagnosed between February 1, 2012 and November 19, 2019 at Peking University Cancer Hospital. Clinical characters were reviewed from patients’ records. Strategies of drugs, progression-free survival (PFS) and OS were collected during the follow-ups. The Kaplan-Meier method and multivariate Cox proportional-hazard analysis were used to conduct the analyses survival and to examine the relationship between the variables and OS. RESULTS: A significantly longer OS was observed either in patients treated with crizotinib [N=106, median OS (mOS): 32.9 months] or in patients treated with a next-generation ALKi [N=34, mOS: not reached (NR)] as the initial ALKi, compared with patients treated with conventional chemotherapy but no ALKi (N=36, mOS: 10.3 months, P

Aim: To investigate the efficacy, safety and optimal dosage of bevacizumab in non-squamous, non-small-cell lung cancer (NSCLC) patients with malignant pleural effusion (MPE). Methods: 20 patients were enrolled and received intrapleural injection of bevacizumab (group A: 2.5 mg/kg d1, d8; group B: 5 mg/kg d1, d8; group C: 7.5 mg/kg d1, d8). Results: The objective response rate (ORR) of MPE was 50%. The median progression-free survival (PFS) of MPE was 7.0 months (95% CI 4.9–9.2). The ORR and PFS of MPE from group B were better than those of group A and group C. The most common adverse events (AEs) were hypertension (15%) and anemia (15%). Conclusion: Bevacizumab has certain efficacy in non-squamous NSCLC patients with MPE. Clinical Trial Registration: NCT02942043 ( ClinicalTrials.gov ).

Objective To explore the impact of venous thromboembolism (VTE) on the diagnosis and treatment of lung cancer patients. Methods We retrospectively analyzed the clinical data of lung cancer patients with VTE treated in Peking University Cancer Hospital. The incidence of VTE was calculated and the relation between VTE and lung cancer was analyzed. Results Among 1766 patients with lung cancer, VTE occurred in 115(6.5%) patients. Among 115 VTE cases, there were 78(67.8%) males patients; 82(71.3%) cases were deep venous thrombosis, 21(18.3%) cases were pulmonary embolism, 12(10.4%) cases were deep venous thrombosis with pulmonary embolism; 74(64.3%) cases were symptomatic VTE; 102(88.7%) patients received antithrombotic therapy. Among the patients who received antithrombotic therapy, 97(95.1%) cases chose drug therapy. In drug treatment, 65(67.0%) cases used adequate/standard dose. Among 115 VTE cases, 52(45.2%) patients had improvement or disappearance of thrombus, 32(27.8%) patients had no improvement, and 31(27.0%) patients with unknown results; 11(9.6%) patients had adverse reactions such as bleeding during antithrombotic therapy; 30(26.1%) patients changed antineoplastic treatment plan due to VTE. Conclusion VTE is a common complication of lung cancer patients. Antithrombotic therapy for lung cancer patients with VTE is complex, the treatment effect is not ideal and the risk of adverse reactions such as bleeding is high. VTE has a great impact on the implementation of anti-cancer treatment.

As a typical non-uniform beam with complex varying cross-section and large curvature, free vibration analysis of flexure hinges in the state-of-the-art compliant mechanisms is challenging due to their complicated and even unsolvable governing differential equation. Investigation on the free vibration analysis of non-uniform beams was attractive in the past but still with a few types of specific beams or approximate solutions. The contribution of this paper is to formulate the dynamic stiffness matrix for generic non-uniform beams and applied for the first time to the free vibration analysis of flexure hinges. Firstly, the vibration solution of general non-uniform Timoshenko beam is derived by using a recursive integral in power series of circular frequency but not the traditional way in the well-known method of Frobenious. Then, the dynamic stiffness matrix of non-uniform Timoshenko beam is derived based on the variational principle. At last, the new method is applied for the free vibration analysis of flexure hinges and flexure-based compliant mechanisms. Several case studies demonstrate the advantage of the proposed approach in terms of high accuracy, generality and high efficiency (only one element is needed). The obtained results are useful for dynamic design of flexure hinges and can serve as a benchmark to examine the accuracy of other numerical solutions. Due to the closed form and universality of the proposed method, it is also of benefit for free vibration analysis of other non-uniform beams with all kinds of varying cross-section or functionally graded beams.

Supplemental material, sj-docx-1-tct-10.1177_15330338211039676 for Pembrolizumab or Bevacizumab Plus Chemotherapy as First-Line Treatment of Advanced Nonsquamous Nonsmall Cell Lung Cancer: A Retrospective Cohort Study by Jie Zhang, Di Wu, Ziran Zhang, Jieran Long, Guangming Tian, Yang Wang, Xiangjuan Ma, Xiaoling Chen, Jindi Han, Weiheng Hu, Ling Dai, Jun Nie and Jian Fang in Technology in Cancer Research & Treatment

Supplemental material, sj-docx-2-tct-10.1177_15330338211039676 for Pembrolizumab or Bevacizumab Plus Chemotherapy as First-Line Treatment of Advanced Nonsquamous Nonsmall Cell Lung Cancer: A Retrospective Cohort Study by Jie Zhang, Di Wu, Ziran Zhang, Jieran Long, Guangming Tian, Yang Wang, Xiangjuan Ma, Xiaoling Chen, Jindi Han, Weiheng Hu, Ling Dai, Jun Nie and Jian Fang in Technology in Cancer Research & Treatment

Supplemental material, sj-docx-4-tct-10.1177_15330338211039676 for Pembrolizumab or Bevacizumab Plus Chemotherapy as First-Line Treatment of Advanced Nonsquamous Nonsmall Cell Lung Cancer: A Retrospective Cohort Study by Jie Zhang, Di Wu, Ziran Zhang, Jieran Long, Guangming Tian, Yang Wang, Xiangjuan Ma, Xiaoling Chen, Jindi Han, Weiheng Hu, Ling Dai, Jun Nie and Jian Fang in Technology in Cancer Research & Treatment

Supplemental material, sj-pdf-3-tct-10.1177_15330338211039676 for Pembrolizumab or Bevacizumab Plus Chemotherapy as First-Line Treatment of Advanced Nonsquamous Nonsmall Cell Lung Cancer: A Retrospective Cohort Study by Jie Zhang, Di Wu, Ziran Zhang, Jieran Long, Guangming Tian, Yang Wang, Xiangjuan Ma, Xiaoling Chen, Jindi Han, Weiheng Hu, Ling Dai, Jun Nie and Jian Fang in Technology in Cancer Research & Treatment

Supplemental material, sj-docx-2-tct-10.1177_15330338211039676 for Pembrolizumab or Bevacizumab Plus Chemotherapy as First-Line Treatment of Advanced Nonsquamous Nonsmall Cell Lung Cancer: A Retrospective Cohort Study by Jie Zhang, Di Wu, Ziran Zhang, Jieran Long, Guangming Tian, Yang Wang, Xiangjuan Ma, Xiaoling Chen, Jindi Han, Weiheng Hu, Ling Dai, Jun Nie and Jian Fang in Technology in Cancer Research & Treatment

Supplemental material, sj-docx-4-tct-10.1177_15330338211039676 for Pembrolizumab or Bevacizumab Plus Chemotherapy as First-Line Treatment of Advanced Nonsquamous Nonsmall Cell Lung Cancer: A Retrospective Cohort Study by Jie Zhang, Di Wu, Ziran Zhang, Jieran Long, Guangming Tian, Yang Wang, Xiangjuan Ma, Xiaoling Chen, Jindi Han, Weiheng Hu, Ling Dai, Jun Nie and Jian Fang in Technology in Cancer Research & Treatment

Supplemental material, sj-docx-1-tct-10.1177_15330338211039676 for Pembrolizumab or Bevacizumab Plus Chemotherapy as First-Line Treatment of Advanced Nonsquamous Nonsmall Cell Lung Cancer: A Retrospective Cohort Study by Jie Zhang, Di Wu, Ziran Zhang, Jieran Long, Guangming Tian, Yang Wang, Xiangjuan Ma, Xiaoling Chen, Jindi Han, Weiheng Hu, Ling Dai, Jun Nie and Jian Fang in Technology in Cancer Research & Treatment

Due to the abundance of organic matter in compost, the addition of compost to soil can promote the adsorption of pesticides. However, few studies have examined the influence of the composting duration on the organic matter (OM) transformation and adsorption capacity of the compost. In this study, a mixture of sewage sludge and straw was composted, and then the physicochemical properties of various OM were studied. Additionally, the sorption capacities of humic acid (HA), humin (HM), humic acid + humin, and fulvic acid (FA) + humic acid + humin extracted from composts of different stages toward pentachlorophenol (PCP) were compared. The sorption data can be well-described by the Freundlich model, and the sorption capacity of PCP on HM is the strongest of all organic components. After 120 days of composting, the sorption abilities of HA and HM increased by 54.76 and 36.73 %, respectively, which corresponds with increases in the aromatization degree, BET specific area, and pore volume and with a decrease in acid functional groups. The sorption ability of HA and HM increased by 54.76 and 36.73 % due to the increase of the aromatization degree. However, the sorption capacity of the compost decreased by 51.2 %, which resulted from a decrease in total organic matter content and from the interaction between organic components in composts. This could be verified by the sequence of the sorption capacity: HM > HM + HA > HM + HA + FA > HA. The contribution of humus to the sorption of PCP onto compost is approximately 41 to 55 %, and it increases with composting time. Therefore, it is possible that other components are present that affect the adsorption of PCP on composts.

Ammonia-oxidising archaea (AOA) are increasingly recognised as the primary mediators of soil ammonia oxidation, particularly in acidic soils. To explore the niche segregation of AOA and ammonia-oxidising bacteria (AOB) and the potential effect of this segregation on nitrification rates and the nitrogen cycle in Chinese agricultural soils, AOA and AOB amoA gene databases were established, and 454 high-throughput sequencing was used to investigate the key factors leading to the niche segregation of these two types of microorganisms. qPCR results demonstrated that there were more functional genes for AOA than for AOB in most of the soils. AOA diversity was higher than AOB diversity in most of the soils with AOA operational taxonomic units (OTU) numbers ranging from 40 to 169 and AOB OTU numbers ranging from 18 to 105. pH was the most important factor influencing the community structure of AOA ( P < 0.01) and AOB ( P < 0.05), and acidophilic AOA (i.e. Nitrosotalea -related sequences) were dominant in soils with pH values below 6.0. In addition, AOA amoA gene copy numbers were significantly positively correlated with pH ( P < 0.05), the ratio of AOA OTU numbers/AOB OTU numbers was significantly negatively correlated with pH ( P < 0.05), and the percentage of sequences represented by the Nitrosotalea cluster was significantly negatively correlated with pH ( P < 0.01).

Manure is one of the most important N sources in paddy rice systems, while it poses a great challenge in meeting rice N requirement and simultaneously reduces adverse environmental impacts. The main objective of this study was to design a simple model for assessing N fate in swine manure amended paddy rice systems. A field experiment was conducted for three cropping seasons to determine the effectiveness of different swine manure amended levels (15%, 30%, and 45% of total N applied) on N transformations and seasonal N fate. Based on field observation data, simulation results clearly showed peaks of various N transformation rates appeared within 2 ~ 3 days after each fertilization. There was an apparent contribution of manure N on N uptake and loss when amount of manure applied was at optimum. However, at supra optimal rate, addition of manure N showed no effect on N uptake of crop and the corresponding N transformations. Across three levels, seasonal ammonia volatilization accounted for 35.6% ~ 38.0% of total N applied, N uptake was 36.7% ~ 41.1%, while N losses via vertical leaching, lateral seepage were 3.9% ~ 4.5% and 4.4% ~ 4.8%, respectively. These results were well predicted by our specific designed model, indicating the model performed effectively at assessing individual transformation process and its associated N fate and help develop efficient management strategies for swine manure amended paddy rice systems.

The concentration and bioavailability of heavy metals in composted organic wastes have negative environmental impacts following land application. Aerobic composting procedures were conducted to investigate the influences of selected parameters on heavy metal speciation and phytotoxicity. Results showed that both of sewage sludge (SSC) and swine manure (SMC) composting systems decreased the pH, the content of organic matter (OM) and dissolved organic carbon (DOC), and total amounts of Cu, Zn and Pb. Sequential extraction showed that readily extractible fractions of exchangeable and carbonate in Cu and Zn increased during SSC composting but decreased during SMC composting, thus their bioavailability factors (BF) enhanced in SSC but declined in SMC. The fraction of reducible iron and manganese (FeMnOX) of Cu and Zn in SSC and FeMnOX-Cu in SMC decreased, but FeMnOX-Zn in SMC gradually increased in the process of compost. In contrast, the changes of Pb distributions were similar in two organic wastes. Pb was preferentially bound to the residual fraction and its BF decreased. The evolution of heavy metal distributions and BF depended on not only total metal concentrations but also the other properties, such as pH, decomposition of OM and decline of DOC. The germination rate (RSG), root growth (RRG) and germination index (GI) of pakchoi (Brassica Chinensis L.) increased during the composting process. Linear regression analysis demonstrated that GI, which could represent phytotoxic behavior to the plants, could be poorly predicted by BF or total amount of metals, i.e., BF-Zn, T-Cu. However, the inclusion of other physicochemical parameters (pH, OM and DOC) could enhance the linear regression significances (R).

The role of surgery in limited small cell lung cancer (SCLC) is still controversial. To assess the role of surgery in SCLC we performed a retrospective analysis of survival in a group of limited stage patients, who were managed with trimodal therapy including surgery, or with chemotherapy and radiotherapy.We performed a retrospective survival analysis in a series of 153 limited stage SCLC patients treated between 1995 and 2013. Kaplan-Meier survival analysis and Cox regression analysis were used to calculate the overall survival of the surgical and non-surgical groups.Median survival in all patients was 21.5 months. Median survival for surgical and non-surgical patients was 30.5 months and 16.9 months, respectively. The survival curves for the two arms are significantly different (P0.01). In multivariate analysis, the benefit of surgical treatment and thoracic radiotherapy varied in a time-dependent fashion.Our results suggest that surgery added to chemotherapy and radiotherapy may be associated with a therapeutic benefit in limited SCLC.

Each time-frequency representation (TFR) has both its own advantages and disadvantages for nonstationary signal analysis. In this paper, an algorithm, nominated as product method, is proposed, which gains one new TFR by the product of two TFRs and integrates their advantages for some applications, especially keeps Wigner distribution's (WD's) auto-term concentration and reduces the crossterms. Potential applications to some TFRs are discussed, such as short time Fourier transform and its spectrogram, Margenau-Hill-spectrogram distribution and WD. Then some instances illustrate that this simple method is valid and practicable, and has much less computational complexity except for the initial TFRs and better visual effect in virtue of auto-term concentration enhancement and cross-term reduction.