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The microstructure, precipitates and properties of 25CrNiMoV (DZ2) steel for high-speed railway axles with different Nb contents were investigated by means of optical microscopy, scanning electron microscopy, electron back-scattering diffraction, transmission electron microscopy and physicochemical phase analysis. The results show that the grain size of the original austenite of the test steels decreases from 20.5 to 14.2 and 10.8 μm after adding 0.026 and 0.039 wt.% Nb to a 25CrNiMoV steel, respectively. Moreover, the block width of the tempered martensite in the test steels is refined from 1.91 to 1.72 and 1.60 µm, respectively. MC-type precipitates in 25CrNiMoV steel are mainly VC, while (Nb,V)C gradually precipitates when Nb is microalloyed, and the amount of precipitates increases with increasing Nb content. Through strengthening mechanism analysis, it is found that grain refinement strengthening is the primary way to increase the strength. The improvement in the yield strength with increasing Nb content is attributed to a significant increase in precipitation strengthening, grain refinement strengthening and dislocation strengthening.

Pulmonary sarcomatoid carcinoma (PSC) is an aggressive and poorly differentiated type of non-small cell lung carcinoma. Because of the rarity of PSC, the efficacy and toxicity of immunotherapy remain unclear. Hence, the aim of this study was to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) for the treatment of advanced PSC. The study cohort was limited to 33 patients with pathologically confirmed PSC treated with ICIs in four hospitals in China from March 2018 to March 2022. Expression of programmed death ligand 1 (PD-L1) was detected by immunohistochemical analysis. Categorical variables were compared with the Fisher exact test and survival analysis was conducted with the Kaplan-Meier method. Of the 33 PSC patients, 8 (24.2%) received monotherapy with ICIs and 25 (75.8%) received combination therapy with ICIs. The objective response rate (ORR) and disease control rate (DCR) were 36.4% and 78.8%, respectively. The median durations of progression-free survival (PFS) and overall survival (OS) were 6.07 and 21.33 months, respectively. PD-L1 status in 16 available samples was assessed, which included 30.3% PD-L1-positive patients. The ORRs for PD-L1-positive vs. -negative patients were 50.0% and 90.0%, the DCR was 33.3% and 83.3%, and the median PFS was 17.50 and 6.07 months, respectively (p=0.812). The median OS was not reached in PD-L1-positive and -negative patients (p=0.655). The incidence of immune-related adverse (irAEs) was 48.5% and mainly included grade 1 or 2 (39.4%), while the incidence of grade 3 or 4 was 9.1%. Pneumonia (9.1%) and skin rash (9.1%) were the most frequent irAEs. Immunotherapy with ICIs was a promising regimen to improve the prognosis of patients with advanced PSC.

Pulmonary involvement has been reported in >40% of autopsy series in patients with metastatic prostate cancer; however, isolated lung metastases have been documented in

Background The eye is a rare site for lung cancer metastasis. Indeed, ocular metastasis is one of the greatest challenges to quality of life in a cancer patient. Here we present a patient with lung adenocarcinoma and ocular metastasis. Case summary The patient was a 70-year-old man diagnosed with lung adenocarcinoma who developed eye metastasis mimicking anterior scleritis. Brain magnetic resonance imaging showed an abnormal signal in the right eye. Based on next generation sequencing of the surgical specimen, the patient was shown to have a KRAS point mutation (p.G12D). Conclusion Multidiscipline expertise collaboration is needed to make the early diagnosis and determine the prompt treatment in patients. We hope to increase the awareness of the possibility of lung cancer metastasizing to the eye.

Background BRAF mutation plays a rare but aggressive oncogenic role in non-small cell lung cancer (NSCLC) patients. The controversy of first-line chemotherapy in patients with different BRAF mutations exists. Here, we identified 41 stage IIIB/IV NSCLC patients with BRAF mutation from 3,669 NSCLC patients by next-generation sequencing (NGS) testing of ctDNA in plasma or tumor tissues. Methods Kaplan-Meier survival curves were used to compare the prognostic difference of progression-free survival (PFS) and overall survival (OS) in different classes of BRAF mutations. Multivariate Cox proportional-hazards regression was used to determine the hazard ratio (HR) of different prognostic factors in survival. Results A total of 40 stage IIIB/IV NSCLC patients with BRAF mutation were further divided into four groups according to the updated functional classification of BRAF mutations, 56.1% (23/41) of class 1, 12.2% (5/41) of class 2, 12.2% (5/41) of class 3 and 19.5% (8/41) of others. The median PFS of patients after first-line pemetrexed-based chemotherapy was longer than other regimens of chemotherapy (7.0 vs. 4.0 months, P

ROS1-rearranged non-small cell lung cancer (NSCLC) is a subset of NSCLC patients with unique malignant behavior and clinical course. Crizotinib, a multi-targeted ALK/ROS1/MET tyrosine kinase inhibitor (TKI), has promising significant activity in NSCLC with ROS1-rearrangement. The next-generation sequencing (NGS) is commonly used to identify the “druggable” genetic alterations in clinical practice. We identified a novel ROS1 fusion variant (FRK-ROS1) in a de novo stage IV NSCLC patient by NGS testing. This novel ROS1-rearrangement is generated by the fusion FRK to ROS1. The patient was remarkably responsive to crizotinib including the brain metastasis. A 29-year-old male never-smoker with chief complaints of back pain with a lumpy and flaky soft tissue mass in the upper right lobe of the lung and diffuse ground-glass shadow in both lungs e IV (cT4N3M1b). A CT-guided biopsy revealed the predominant adenocarcinoma and partial mucinous adenocarcinoma. By using next-generation sequencing (NGS) assay, we found that the tumor had FRK-ROS1 fusion rather than other actionable mutations. In that case, the patient took the first-line crizotinib and experienced a remarkable tumor response to it and tolerance well until written. FRK-ROS1 is a novel ROS1 fusion variant in NSCLC identified by NGS testing and the first-line crizotinib showed excellent performance in all lesions including the brain metastasis.

Background: Administering corticosteroid is an effective therapeutic strategy for treating most inflammatory conditions. However, there is a chance for corticosteroid treatment to adversely affect bones, resulting in corticosteroid-induced osteoporosis, which is a highly prevalent type of secondary osteoporosis. Elevated bone resorption and reduced formation of bone are pathogenesis indicators of corticosteroid-induced osteoporosis. Preventative therapy is recommended for patients initiating steroids. This study aims to evaluate the efficiency of calcium and vitamin D in treating adults diagnosed with osteoporosis caused by corticosteroid therapy. Methods: Electronic databases will be searched systematically to source studies that have evaluated the efficiency of calcium and vitamin D as a treatment method for adult patients with osteoporosis from corticosteroid therapy. The databases include, PubMed, EMBASE, the Cochrane Library, Scopus, and Web of Science. The timeline of the search will be limited from inception to November 2020. This study will utilize the Cochrane risk of bias tool to assess the quality of the studies reviewed. Moreover, appropriate methods will be chosen to analyze the data. The RevMan 5.3 software is utilized to perform statistical analysis. Results: This study will provide additional practical and targeted results of evaluating the efficiency of calcium and vitamin D in treating adults with corticosteroid-induced osteoporosis. Conclusion: The results of this study will provide further evidence about calcium and vitamin D in treating adults with corticosteroid-induced osteoporosis, clinicians and policymakers can make practical use of the results. Ethics and dissemination: Since this systematic review does not involve any human or animal participants, an ethics approval is not required. Systematic review registration: Aug 19, 2021. osf.io/zvb38. (https://osf.io/zvb38/).

Background: Whether or not EGFR mutation status detected by ddPCR in plasma predicts the effect of icotinib on patients with advanced lung adenocarcinoma was determined. Methods: Plasma and matched tissue specimens from patients with advanced lung adenocarcinoma were collected prior to icotinib treatment. The ARMS method was used to detect EGFR mutation status in DNA extracted from tissue specimens, while the EGFR mutation status in ctDNA extracted from plasma specimens was determined by ddPCR. The therapeutic effects of icotinib were compared between patients with EGFR - activating mutations detected by ddPCR in ctDNA and ARMS in tissue DNA. Results: EGFR mutation status was detected in 96 tissue and 100 plasma specimens. The sensitivity and positive predictive value of 19del detected in ctDNA by ddPCR was 70.97% (22/31) and 44.90% (22/49), respectively. The positive predictive value was 84.62% (22/26) and the sensitivity was 53.66% (22/41) for the L858R mutation. For the common sensitive EGFR mutations, ddPCR had a positive predictive value of 77.19% (44/57) and a sensitivity of 48.89% (44/90). Patients with sensitive EGFR mutations in ctDNA had objective response and disease control rates (DCR) similar to patients who had sensitive EGFR mutations in tissues detected by ARMS when treated with icotinib (57.14% vs . 51.51% and 92.86% vs . 90.91%, respectively). Conclusions: Patients with sensitive EGFR mutations in plasma specimens detected with ddPCR had a higher ORR and DCR compared with patients with sensitive EGFR mutations in tissue detected with the ARMS method.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths. Compound K, an active metabolite of ginsenosides, is reported to exhibit anti-cancer property in various types of human malignancies. The present study investigated the role of compound K on glucose metabolism in NSCLC cells and its underlying mechanism. Our study found that compound K dose-dependently inhibited the cell viability of NSCLC cells. Moreover, administration with compound K decreased glucose uptake and lactate secretion under normoxic and hypoxic conditions. Consistently, the expression of key enzymes (HK II, PDK1 and LDHA) involved in glucose metabolism were inhibited in compound K-treated tumor cells. In addition, compound K inhibited the expression of HIF-1α and its downstream gene GLUT1. On the contrary, overexpression of HIF-1α elevated metabolic reactions and partly attenuated the inhibitory role of compound K on NSCLC cell growth. These results demonstrate that compound K suppresses NSCLC cell growth via HIF-1α mediated metabolic alteration, contributing to novel anticancer therapy by targeting glucose metabolism.

BACKGROUND: Chemotherapy is the major choice for advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor exon 20 insertion (EGFR ex20ins). The efficacy of pemetrexed-based with other chemotherapy regimens and EGFR ex20ins subtypes in this population has not been well studied. METHODS: We screened patients with EGFR ex20ins by next-generation sequencing (NGS) from a large cohort. The clinicopathologic and medical information were collected in advanced NSCLC patients with EGFR ex20ins. We also compared the clinical outcomes among patients with different subtypes of EGFR ex20ins. RESULTS: We retrospectively collected 119 stage IIIB/IV NSCLC patients with EGFR ex20ins from 9142 NSCLC patients across China from June 2013 to December 2018. The subtypes of EGFR ex20ins included A767_V769dupASV (33/119, 27.73%), S768_D770dupSVD (19/119, 15.97%), N771_H773dupNPH (11/119, 9.24%), A763_Y764insFQEA (2/119, 1.68%) and others (54/119, 45.38%). A total of 64.7% (77/119) of patients received pemetrexed-based first-line chemotherapy and 13.45% (16/119) of patients received pemetrexed-based second-line chemotherapy. Pemetrexed-based chemo-treated patients had longer median progression-free survival (PFS) than patients without pemetrexed-based chemo-treated (5.5 vs. 3.0 months, P=0.0026). Survival data was available for 66 patients and the median overall survival (OS) was 24.7 months. Pemetrexed-based chemo-treated patients had longer OS tendency than patients without pemetrexed-based chemo-treated (25.0 vs. 19.6 months, P=0.0769). Patients harboring A767_V769dupASV had better OS than other subtypes of EGFR ex20ins but without statistical significance (P=0.0676). Multivariate analysis revealed that histological type of NSCLC and bone-metastasis before treatment were independent prognostic factors for OS in all patients after adjusting all characteristic and treatment factors (P

Background: High frequency of MNNG HOS transforming (MET) exon 14 skipping mutation (MET exon 14Δ) has been reported in pulmonary sarcomatoid carcinomas (PSCs). However, the frequencies differ greatly. Our study aims to investigate the frequency of MET alterations and the correlations among MET exon 14Δ, amplification, and protein overexpression in a large cohort of PSCs. MET exon 14Δ, amplification, and protein overexpression were detected in 124 surgically resected PSCs by using Sanger sequencing, fluorescent in situ hybridization (FISH), and immunohistochemistry (IHC) respectively. MET exon 14Δ was identified in 9 (7.3%) of 124 cases, including 6 pleomorphic carcinomas, 2 spindle cell carcinomas and 1 carcinosarcoma. MET amplification and protein overexpression were detected in 6 PSCs (4.8%) and 25 PSCs (20.2%), respectively. MET amplification was significantly associated with overexpression (P

This study aimed to systematically evaluate the value of combined detection of serum CEA and CA125 concentrations for the diagnosis of lung cancer. Related studies regarding the diagnosis of lung cancer were searched in PubMed, Embase, CNKI, and Wanfang using a computer. The number of patients who were true-positive, false-positive, false-negative, and true-negative were extracted from each study. Meta-analysis was performed using the Meta-Disc l.4, RevMan 5.3. Seven studies involving 2,216 cases were finally included. Regarding the diagnosis of lung cancer, the sensitivity, specificity, and diagnostic odds ratio of combined CEA and CA125 detection were higher than those of CEA detection alone. The area under the curve (AUC) of combined detection was 0.90, whereas the independently detected AUC was 0.73. Combined CEA and CA125 detection has higher diagnostic efficiency for lung cancer than CEA detection alone. The significance of combined serum CEA and CA125 detection in lung cancer is confirmed.

BACKGROUND RET rearrangements have been reported in 30% of papillary thyroid carcinomas and 1-2% of non-small cell lung cancer (NSCLC). In these tumors, RET gene fusion product provides a constitutively active tyrosine kinase (TKR), leading to uncontrolled cellular proliferation, differentiation, and migration. In this investigation we assessed the positivity rate of RET gene rearrangement in primary and metastatic non-small cell lung cancer and explored their relationships. MATERIAL AND METHODS Between January 2013 and May 2015, we collected 384 cases of primary metastatic non-small cell lung cancer, which included 246 matched metastatic tumors cases from multiple centers. The RET rearrangement uniformity in metastatic lymph nodes and tumor specimens were contrasted and the relationships between RET rearrangement and patients' clinical features were investigated. RESULTS For those 384 cases, 7 (1.82%) cases had tumors with identified RET rearrangement. Among the 246 paired cases, 3 (1.22%) cases of primary tumor had identified RET rearrangement and 2 (0.81%) cases of metastases had identified RET rearrangement. The sensitivity was 66.67% (2/3) and the specificity was 100% (243/243). CONCLUSIONS The results of this research indicate that the metastases of non-small cell lung cancer can predict RET rearrangement of the primary tumor tissue in the majority of cases. Testing for RET rearrangement in metastases can be used as an alternative to testing of primary tumor tissue if it is inaccessible.

Small intestinal metastases from primary lung cancer are rare. Such patients have a poor prognosis. Early diagnosis of small intestinal metastases is difficult because of the low incidence of clinically apparent symptoms. The standard treatment for small intestinal metastases has not been established. A 69-year-old Chinese man presented for evaluation of a tumor in the right lower lung and mediastinal lymph node enlargement on clinical examination. The clinical stage was cT2N2M0 (stage IIIA). Histologic examination of the tumor revealed lung adenocarcinoma. He could not tolerate surgery; hence, he received two chemotherapy regimens. However, the disease progressed. He had bloating after chemotherapy and decreased flatus. An abdominal CT scan showed an intestinal effusion with local intestinal obstruction. Medical treatment was ineffective; hence, he underwent a diagnostic laparoscopy. The pathologic evaluation suggested an intestinal metastatic adenocarcinoma from the primary lung cancer. Based on an real-time PCR assay, the tumor had a ROS1 fusion and responded well to crizotinib. The progression-free survival was 7 months. Physicians must be aware of the possibility of intestinal metastases from primary lung cancer. With an accurate diagnosis and thorough evaluation, patients may benefit from targeted therapy.

ALK rearrangement is a driver gene in non-small cell lung cancer (NSCLC). ALK-positive tumors are sensitive to ALK-tyrosine kinase inhibitors (TKIs). The detection of key driver genes is crucial to enable personalized treatment. Different histomorphological patterns have different driver genes. Herein, we report the case of a 42-year-old male patient diagnosed with adenocarcinoma with different histomorphologies in the primary lung site (mucinous type) and lymph node metastasis (solid type), of the same genotype, both presenting with ALK rearrangement but negative for EGFR mutation. This histological heterogeneity did not necessarily indicate a genomic difference. Genomic analysis may be a supplement to the histological features of ALK-rearranged tumors. These gene alterations could aid the choice of an appropriate TKI and predict therapeutic response.

ROS1 rearrangement is a validated therapeutic driver gene in non-small cell lung cancer (NSCLC) and represents a small subset (1-2%) of NSCLC. A total of 17 different fusion partner genes of ROS1 in NSCLC have been reported. The multi-targeted MET/ALK/ROS1 tyrosine kinase inhibitor (TKI) crizotinib has demonstrated remarkable efficacy in ROS1-rearranged NSCLC. Consequently, ROS1 detection assays include fluorescence in situ hybridization, immunohistochemistry, and real-time PCR. Next-generation sequencing (NGS) assay covers a range of fusion genes and approaches to discover novel receptor-kinase rearrangements in lung cancer. A 63-year-old male smoker with stage IV NSCLC (TxNxM1) was detected with a novel ROS1 fusion. Histological examination of the tumor showed lung adenocarcinoma. NGS analysis of the hydrothorax cellblocks revealed a novel CEP72-ROS1 rearrangement. This novel CEP72-ROS1 fusion variant is generated by the fusion of exons 1-11 of CEP72 on chromosome 5p15 to exons 23-43 of ROS1 on chromosome 6q22. The predicted CEP72-ROS1 protein product contains 1202 amino acids comprising the N-terminal amino acids 594-647 of CEP72 and C-terminal amino acid 1-1148 of ROS1. CEP72-ROS1 is a novel ROS1 fusion variant in NSCLC discovered by NGS and could be included in ROS1 detection assay, such as reverse transcription PCR. Pleural effusion samples show good diagnostic performance in clinical practice.

We report a case of concomitant EML4-ALK and TPM3-ROS1 fusion in non-small cell lung cancer (NSCLC) in a 47-year-old Chinese man and review the clinical characteristics of this type double of fusion. The patient presented with a local tumor of the left upper lobe and underwent thoracoscopy. Postoperative surgical pathologic staging revealed T1a N0 M0 stage IA. Histological examination of the tumor showed lung adenocarcinoma. Ventana ALK (D5F3) assay of the left lung tissue was ALK negative; however, immunohistochemical assay was positive for ROS1 protein. Using next generation sequencing, we found that the tumor had concomitant EML4-ALK and TPM3-ROS1 fusion. No recurrence was observed during seven months of follow-up. Precise diagnostic techniques allow the detection of concomitant ROS1 fusion and other driver genes, including ALK or EGFR; therefore oncologists should consider this rare double mutation in NSCLC patients. Further exploration of treatment models is required to provide additional therapeutic options.

Lung adenocarcinomas with gene rearrangement in the receptor tyrosine kinase ROS1 have emerged as a rare molecular subtype. Although these lung adenocarcinomas respond to ROS1tyrosine kinase inhibitors, many patients ultimately acquire resistance. ROS1gene rearrangement is generally mutually exclusive with other driver genomic alterations, such as those in EGFR, KRAS, or ALK, thus multiple genomic alterations are extremely rare. Herein, we report a case of a 42-year-old man diagnosed with lung adenocarcinoma positive for a SDC4-ROS1 fusion, who was treated with crizotinib followed by three cycles of chemotherapy. A biopsy acquired after disease progression revealed the original SDC4-ROS1 fusion along with a KRAS point mutation (p.G12D).We reviewed the related literature to determine the frequency of gene mutations in non-small cell lung cancer patients. A better understanding of the molecular biology of non-small cell lung cancer with multiple driver genomic aberrations will assist in determining optimal treatment.

ROS1 rearrangement occurs in 1–2% of non-small cell lung cancer (NSCLC) cases. These patients would benefit from treatment with the anaplastic lymphoma kinase inhibitor, crizotinib; however, resistance to crizotinib inevitably develops in such patients despite an initial response. The mechanism of acquired resistance to crizotinib in patients with NSCLC with ROS1 rearrangement has not yet been identified. Herein, we report a case of a 66-year-old woman diagnosed with adenocarcinoma. PCR revealed no EGFR or ALK mutations. After the patient underwent several rounds of chemotherapy, crizotinib was administered. The disease explosively progressed six months later. A novel PIK3CA gene point mutation (p.L531P) was detected by next generation sequencing. This case is the second report of bypass activation conferred crizotinib resistance in a patient with NSCLC with ROS1-rearrangement, but is the first to confirm that activation of the mTOR signaling pathway leads to acquired crizotinib resistance.

Background c-MET has recently been identified as a promising novel target in non-small cell lung cancer (NSCLC). We detected the consistency of c-MET gene amplification in metastatic lymph nodes and tumor tissues of NSCLC patients and discuss the clinical application value of c-MET gene amplification in metastatic lymph nodes. Methods Real-time fluorescent quantitative PCR was used to test tumor tissues in 368 NSCLC patients and 178 paired metastatic lymph node samples. The amplification consistency in metastatic lymph nodes and tissue samples were compared and the correlation between c-MET gene amplification and the clinical characteristics of patients was analyzed. Results The c-MET gene amplification rate was 8.97% (33/368) in tumor tissues. Of the 178 paired cases, c-MET gene amplification was positive in 7.95% (15/178) of cancerous tissues and 18.54% (33/178) of metastatic lymph nodes. c-MET gene amplification was detected more frequently in metastatic lymph nodes than in primary cancerous tissue. When metastatic lymph nodes were used as surrogate samples of primary cancerous tissues, the sensitivity was 86.67% (13/15) and the specificity was 87.69% (143/163). Conclusions Screening for c-MET gene amplification in lymph node metastases could determine which patients are eligible for tyrosine kinase inhibitor therapy. Lymph node metastasis can predict c-MET gene amplification in a primary tumor and guide the clinical use of c-MET gene targeted drugs.

Anaplastic lymphoma kinase (ALK) rearrangement responds to ALK tyrosine kinase inhibitors (TKIs) in lung cancer. Many cases ultimately acquire resistance to crizotinib. Resistance, including ALK-dominant or ALK non-dominant, mechanisms have been described. Transformation to small-cell lung cancer is rare. Herein, we report a 49-year-old man diagnosed with adenocarcinoma, who was negative for EGFR and ALK genes as detected by reverse transcription polymerase chain reaction, and was treated with crizotinib. A new biopsy showed a small-cell lung cancer after disease progression. Then, next-generation sequencing (NGS) was carried out and detected a TP53 gene mutation, an ALK rearrangement, and no loss of the retinoblastoma gene (RB). Although a regimen for small-cell lung cancer may be one treatment option, a heterogeneous tumor may exist at the time of diagnosis and manifest during the course of disease.

Background Primary malignant melanoma of the esophagus (PMME) is rare with high malignancy and poor prognosis. The aim of this study was to investigate the relationship between prognosis and clinicopathological characteristics of this disease. Methods A total of 9 patients with PMME were treated in Zhejiang Cancer Hospital between 2009 and 2019 retrospectively. According to 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction, none of the patients were in stage I. However, 5 patients were in stage II, 2 patients were in stage III, and 2 patients were in stage IV at diagnosis. Five patients received surgery, while one of them received palliative resection. Three patients received postoperative chemotherapy; two of them (2/5) were diagnosed with recurrence. One patient in stage II received targeted therapy. One patient in stage III received first line chemotherapy and efficacy evaluation was stable disease (SD). Another one in stage III received biotherapy. One patient in stage IV received Chinese Medicine treatment and another received chemotherapy and palliative surgery. Results The 1-year disease-free survival (DFS) and overall survival (OS) rates of stage II who received surgery were 50% (2/4) and 100% (4/4) respectively. The 2-year DFS and OS rates were 50% (2/4) and 75% (3/4), respectively. However, patients with stage III–IV have a very poor prognosis. The 1-year OS is 0%. Conclusions Due to the small sample size, the statistic efficacy is low, but it can provide a certain theoretical basis for future research.

Background Whether or not EGFR mutation status detected by ddPCR in plasma predicts the effect of icotinib on patients with advanced lung adenocarcinoma was determined. Methods Plasma and matched tissue specimens from patients with advanced lung adenocarcinoma were collected prior to icotinib treatment. The ARMS method was used to detect EGFR mutation status in DNA extracted from tissue specimens, while the EGFR mutation status in ctDNA extracted from plasma specimens was determined by ddPCR. The therapeutic effects of icotinib were compared between patients with EGFR-activating mutations detected by ddPCR in ctDNA and ARMS in tissue DNA. Results EGFR mutation status was detected in 96 tissue and 100 plasma specimens. The sensitivity and positive predictive value of 19del detected in ctDNA by ddPCR was 70.97% (22/31) and 44.90% (22/49), respectively. The positive predictive value was 84.62% (22/26) and the sensitivity was 53.66% (22/41) for the L858R mutation. For the common sensitive EGFR mutations, ddPCR had a positive predictive value of 77.19% (44/57) and a sensitivity of 48.89% (44/90). Patients with sensitive EGFR mutations in ctDNA had objective response and disease control rates (DCR) similar to patients who had sensitive EGFR mutations in tissues detected by ARMS when treated with icotinib (57.14% vs. 51.51% and 92.86% vs. 90.91%, respectively). Conclusions Patients with sensitive EGFR mutations in plasma specimens detected with ddPCR had a higher ORR and DCR compared with patients with sensitive EGFR mutations in tissue detected with the ARMS method.

C-ros oncogene 1 receptor tyrosine kinase (ROS1) rearrangement forms a novel molecular subgroup of non-small cell lung cancer (NSCLC). The present study explored the clinicopathological features and clinical efficacy of crizotinib in patients with ROS1-positive NSCLC. A retrospective analysis of 2,617 cases of NSCLC diagnosed between January 2013 and December 2016 was performed. ROS1 fusion genes were detected by reverse transcription-quantitative polymerase chain reaction, fluorescence in situ hybridization or next-generation sequencing techniques, and patients positive for the ROS1 fusion gene received oral treatment with crizotinib. The ROS1 fusion was identified in 67 out of 2,617 cases (2.56%), including 21 cases that were male and 46 cases that were female. The median age was 68 years. Among these cases, 59 (88.06%) were adenocarcinoma and 8 were non-adenocarcinoma. According to Tumor-Node-Metastasis (TNM) staging, 4 cases were stage I–IIIa and 63 (94.02%) were stage IIIb–IV. The epidermal growth factor receptor (EGFR) gene status included 60 cases of wild-type, 1 case of co-mutation and 6 unknown cases. Statistically significant differences were identified for sex, TNM staging and EGFR gene status between ROS1 fusion gene-positive and -negative patients (P

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths. Compound K, an active metabolite of ginsenosides, is reported to exhibit anti-cancer property in various types of human malignancies. The present study investigated the role of compound K on glucose metabolism in NSCLC cells and its underlying mechanism. Our study found that compound K dose-dependently inhibited the cell viability of NSCLC cells. Moreover, administration with compound K decreased glucose uptake and lactate secretion under normoxic and hypoxic conditions. Consistently, the expression of key enzymes (HK II, PDK1 and LDHA) involved in glucose metabolism were inhibited in compound K-treated tumor cells. In addition, compound K inhibited the expression of HIF-1α and its downstream gene GLUT1. On the contrary, overexpression of HIF-1α elevated metabolic reactions and partly attenuated the inhibitory role of compound K on NSCLC cell growth. These results demonstrate that compound K suppresses NSCLC cell growth via HIF-1α mediated metabolic alteration, contributing to novel anticancer therapy by targeting glucose metabolism.

Many studies conducted on the relationship between serum iron levels and lung cancer risk had produced inconsistent results. We therefore conducted a meta-analysis to determine whether serum iron levels were lower in lung cancer patients compared to those in controls.A literature survey was conducted by searching the PubMed, WanFang, CNKI, and SinoMed databases for articles published as of Mar 1, 2018. Standard mean differences (SMD) with the corresponding 95% confidence intervals (CI) were executed by Stata 12.0 software. A total of 13 publications involving 1118 lung cancer patients and 832 controls were included in our study. The combined results showed that serum iron levels in lung cancer cases had no significantly lower when compared to those in controls [summary SMD = -0.125, 95%CI= -0.439, 0.189, Z = 0.78, p for Z test= 0.435], with high heterogeneity (I2= 89.9%, P< 0.001) found. In the stratified analysis by geographic locations, consistent results were found for serum iron levels between lung cancer patients and controls both in Asian populations [summary SMD = -0.113, 95%CI= -0.471, 0.245] and European populations [summary SMD = -0.215, 95%CI= -0.835, 0.404]. Publication bias was not found when evaluated by Begg's funnel plot and Egger's regression asymmetry test.In summary, the current study showed that serum iron levels had no significant association on lung cancer risk.

Accumulating evidences have indicated that BIM expression largely decides the development of lung cancer and outcome of EGFR-mutant lung cancers after TKI treatments. BIM polymorphism is a 2,903-bp deletion in the second exon. To clarify the relationship between this BIM polymorphism and clinical outcomes of lung cancers, we conducted this meta-analysis and observed the survival and responses to TKIs. Sixteen cohort studies, covering 4393 WT and 916 BIM deletion patients were included. Overall, BIM deletion polymorphism was associated with significantly shorter progression-free survival (PFS) and slightly shorter overall survival (OS), compared to the WT group. Moreover, patients with BIM deletion polymorphism showed significantly inferior response to EGFR TKIs. In conclusion, our analysis confirmed that lung cancer patients harboring the BIM deletion have inferior survival and TKI responses. Examination of the novel biomarker BIM deletion in lung cancer patients, especially for the EGFR mutant cohort, could provide some prognostic utility.

Lung adenocarcinomas with gene rearrangement in the receptor tyrosine kinase ROS1 have emerged as a rare molecular subtype. Although these lung adenocarcinomas respond to ROS1tyrosine kinase inhibitors, many patients ultimately acquire resistance. ROS1gene rearrangement is generally mutually exclusive with other driver genomic alterations, such as those in EGFR, KRAS, or ALK, thus multiple genomic alterations are extremely rare. Herein, we report a case of a 42‐year‐old man diagnosed with lung adenocarcinoma positive for a SDC4‐ROS1 fusion, who was treated with crizotinib followed by three cycles of chemotherapy. A biopsy acquired after disease progression revealed the original SDC4‐ROS1 fusion along with a KRAS point mutation (p.G12D).We reviewed the related literature to determine the frequency of gene mutations in non‐small cell lung cancer patients. A better understanding of the molecular biology of non‐small cell lung cancer with multiple driver genomic aberrations will assist in determining optimal treatment.

Background c‐MET has recently been identified as a promising novel target in non‐small cell lung cancer (NSCLC). We detected the consistency of c‐MET gene amplification in metastatic lymph nodes and tumor tissues of NSCLC patients and discuss the clinical application value of c‐MET gene amplification in metastatic lymph nodes. Methods Real‐time fluorescent quantitative PCR was used to test tumor tissues in 368 NSCLC patients and 178 paired metastatic lymph node samples. The amplification consistency in metastatic lymph nodes and tissue samples were compared and the correlation between c‐MET gene amplification and the clinical characteristics of patients was analyzed. Results The c‐MET gene amplification rate was 8.97% (33/368) in tumor tissues. Of the 178 paired cases, c‐MET gene amplification was positive in 7.95% (15/178) of cancerous tissues and 18.54% (33/178) of metastatic lymph nodes. c‐MET gene amplification was detected more frequently in metastatic lymph nodes than in primary cancerous tissue. When metastatic lymph nodes were used as surrogate samples of primary cancerous tissues, the sensitivity was 86.67% (13/15) and the specificity was 87.69% (143/163). Conclusions Screening for c‐MET gene amplification in lymph node metastases could determine which patients are eligible for tyrosine kinase inhibitor therapy. Lymph node metastasis can predict c‐MET gene amplification in a primary tumor and guide the clinical use of c‐MET gene targeted drugs.

The experimental treatment of emulsifying wastewater containing fluo- rescent permeating agent is conducted using demulsification, flocculation, sedimentation and Fenton processes. The experimental results show that, under the appropriate conditions, the COD, oil and chromaticity can be removed efficiently. The pH, COD, oil and chromaticity of the outwater can reach the national standards.

In handwritten character recognition, it is a significant step to segment a text line into characters. The unsupervised clustering is a common approach for this task. However, due to the strong overlapping and touch among characters, the separation boundaries between two characters are usually nonlinear, which leads to the failure of the widely used clustering methods such as k-means. To tackle this problem, this paper proposes a new handwritten character segmentation method based on nonlinear clustering methods. In the proposed approach, we first segment the entire text line into strokes, the similarity matrix of which is computed according to stroke gravities. Then, the nonlinear clustering methods are performed on this similarity matrix to obtain cluster labels for these strokes. According to the obtained cluster labels, the strokes are combined to form characters. In this paper, we consider two nonlinear clustering methods, namely, spectral clustering based on Normalized cut (Ncut) and kernel clustering based on Conscience On-Line Learning (COLL). Whereby, two segmentation approaches are proposed with the one using Ncut termed SegNcut, and the one using COLL termed SegCOLL. Experiments on four databases are conducted to demonstrate the effectiveness of our SegNcut and SegCOLL approaches.

Due to the low density and high specific strength, magnesium and its alloys have been extensively used in the automobile and aerospace applications, where the weight reduction is critical. However, they are highly prone to corrosion, which has greatly limited their application in the automotive and aerospace industries. This paper briefly reviews the technologies for improving the corrosion and wear resistance of magnesium alloys and finds that the widespread application of magnesium alloys is still limited by the lack of proper protective coatings. Therefore, there is still a need to explore new materials and methods for the effective protection of magnesium and its alloys.