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BackgroundBarrier-to-autointegration factor 1 (BANF1) is an abundant and ubiquitously expressed postnatal mammalian protein that is overexpressed in numerous human cancers and can promote cancer cell proliferation. However, the role of BANF1 in prognosis remains unclear in head and neck squamous cell carcinoma (HNSCC).MethodsBANF1 expression data were obtained from the GEO and TCGA databases. We used Cox regression and Kaplan–Meier curves to assess the prognostic potential of BANF1. The role of BANF1-related genes was investigated using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses. In addition, we explored the link between BANF1, drug sensitivity, and the tumor immune microenvironment. Finally, functional in vitro and in vivo assays were used to explore the effects of BANF1 on tumor growth and metastasis of HNSCC.ResultsBANF1 was markedly overexpressed in HNSCC and was correlated with clinicopathological characteristics. According to survival analysis, BANF1 can be inversely correlated with patient survival and can act as a prognostic risk indicator. IC50 values for chemotherapeutic treatments indicated that the group with high BANF1 expression was more responsive to most antitumor treatments. Furthermore, higher TIDE scores were observed in the low BANF1 expression group, indicating a decline in the efficacy of immune checkpoint inhibitor therapy. Functionally, the malignant biological behavior of HNSCC cell lines was inhibited when BANF1 expression was knocked down.ConclusionBANF1 can promote tumor progression in patients with HNSCC. BANF1 shows great promise as a potential biomarker to assess the prognosis.

Abstract Radioresistance imposes a great challenge in reducing tumor recurrence and improving the clinical prognosis of individuals having oral squamous cell carcinoma (OSCC). OSCC harbors a subpopulation of CD44(+) cells that exhibit cancer stem-like cell (CSC) characteristics are involved in malignant tumor phenotype and radioresistance. Nevertheless, the underlying molecular mechanisms in CD44( + )-OSCC remain unclear. The current investigation demonstrated that methyltransferase-like 3 (METTL3) is highly expressed in CD44(+) cells and promotes CSCs phenotype. Using RNA-sequencing analysis, we further showed that Spalt-like transcription factor 4 (SALL4) is involved in the maintenance of CSCs properties. Furthermore, the overexpression of SALL4 in CD44( + )-OSCC cells caused radioresistance in vitro and in vivo. In contrast, silencing SALL4 sensitized OSCC cells to radiation therapy (RT). Mechanistically, we illustrated that SALL4 is a direct downstream transcriptional regulation target of METTL3, the transcription activation of SALL4 promotes the nuclear transport of β-catenin and the expression of downstream target genes after radiation therapy, there by activates the Wnt/β-catenin pathway, effectively enhancing the CSCs phenotype and causing radioresistance. Herein, this study indicates that the METTL3/SALL4 axis promotes the CSCs phenotype and resistance to radiation in OSCC via the Wnt/β-catenin signaling pathway, and provides a potential therapeutic target to eliminate radioresistant OSCC.

The SARS-CoV-2 evolution trajectory remains uncertain, and the antigenic characteristics of future variants are highly unpredictable. We report the immunogenicity and safety of multivalent COVID-19 vaccines, SCTV01E and SCTV01E-1, against Omicron BA.5. This phase 2 trial randomized 400 adults into two cohorts, 160 unvaccinated (3 doses) and 240 previously vaccinated (2 doses) individuals to receive 30 µg SCTV01E-1 or 30 µg SCTV01E (1:1) between 4 November and 28 November 2022. Among the unvaccinated cohort, day 42 geometric mean fold rises (GMFRs) of neutralizing antibodies (nAb) against Omicron BA.5 were reported to be 12.8× and 20.5× over day 0 for SCTV01E-1 and SCTV01E, respectively. On day 178, both vaccines increased geometric mean titers (GMTs) of nAb against BA.5 following the booster dose compared to pre-booster levels on D150. Similar frequencies of solicited [6.2% (5/81) and 7.6% (6/79)] and unsolicited [11.1% (9/81) and 10.1% (8/79)] adverse events (AEs) were reported in SCTV01E-1 and SCTV01E groups, respectively. Grade 3 or more AEs were < 2% in both vaccine groups [SCTV01E-1: 1.2% (1/81), SCTV01E: 1.3% (1/79)]. In the previously vaccinated cohort, similar GMFRs were reported on day 28 (SCTV01E-1: 9.4× and SCTV01E: 8.7×) over baseline (D0). On day 148, both vaccines showed increased nAb levels with similar GMFRs over D120. Comparable incidences of solicited [13.2% (16/121) and 10.9% (13/119)] and unsolicited [17.4% (21/121) and 10.9% (13/119)] AEs were reported in SCTV01E-1 and SCTV01E groups, respectively. Numerically identical ≥ grade 3 AEs [SCTV01E-1: 1.7% (2/121) and SCTV01E: 1.7% (2/119)] were reported. This trial demonstrates the effectiveness of updated multivalent vaccines with acceptable safety profiles.

In Internet of vehicles (IoV), vehicle-oriented applications are generally computation-intensive and latency-sensitive.Introducing idle computing resources from mobile vehicles as a supplement to network computing power can effectively alleviate the load pressure on edge servers.The problem of task allocation for edge computation offloading in the context of IoV environment were researched.By fully leveraging the combined computing resources of roadside units (RSU), user vehicles, and mobile vehicles within the RSU service range, a computation offloading strategy based on the sparrow search algorithm was proposed and referred to as sparrow search based computation offloading scheme (S2COS), aiming to optimize the overall system energy consumption.In addition, this strategy fully taked into account practical network issues such as service time constraints caused by vehicle mobility and the potential occurrence of computation node failures.The simulation results demonstrate that S2COS can meet the latency requirements for computation-intensive and latency-sensitive tasks, while significantly reducing system energy consumption.

The Uhelchulu quartz diorite-granodiorite intrusions in Xiwuqi, Inner Mongolia, are exposed along the northwestern margin of the Xilinhot microcontinental block, located within the central and eastern parts of the southeastern Hegenshan suture zone. LA-ICP-MS zircon U-Pb dating yielded crystallization ages of (396 ± 8) Ma for the quartz diorite and (385 ± 5) Ma for the granodiorite, indicating an Early-Middle Devonian magmatic event. The quartz diorite exhibits I-type granite features, characterized by elevated Al2O3 (14.33–15.43 wt%), MgO (3.73–5.62 wt%), and Na (Na2O/K2O = 1.04–1.44), coupled with low P2O5 (0.15–0.20 wt%) and TiO2 (0.73–0.99 wt%). Trace element patterns show relative enrichments in Rb, Th, U, and Pb, while Nb, Ta, Sr and Ti are relatively depleted. Total REE contents are relatively low (123–178 ppm), with significant LREE enrichment (ΣLREE/ΣHREE = 4.75–5.20), and a non-obvious Eu anomaly (δEu = 0.75–0.84). In contrast, the granodiorite displays S-type granite characteristics, with high SiO2 (70.48–73.01 wt%), K (K2O/Na2O = 1.35–1.83), Al2O3 (A/CNK = 1.16–1.31), and a high differentiation index (DI = 76–82). Notably, MgO (1.44–2.24 wt%) contents are low, and significant depletions of Ba, Sr, Ti, and Eu are observed, while Rb, Pb, Th, U, Zr, and Hf are significantly enriched. Total REE contents are relatively low (178–314 ppm), exhibiting significant LREE enrichment (LREE/HREE = 6.17–8.36) and a pronounced negative Eu anomaly (δEu = 0.34–0.49). The overall characteristics point towards an active continental margin arc background for the Uhelchulu intrusions. Previous studies have suggested that the Hegenshan ocean continuously subducted northward from the Early Carboniferous to the Late Permian, but there is a lack of evidence for its geological evolution during the pre-Early Carboniferous. Therefore, this paper provides a certain basis for studying the geological evolution during the pre-Early Carboniferous in the Hegenshan ocean. We preliminarily believed that the Hegenshan ocean underwent a southward subduction towards the Xilinhot microcontinental block in the Xiwuqi area, at least from the Early Devonian to the Middle Devonian and the Hegenshan ocean may might have undergone a shift in subduction mechanism during the Late Devonian or Early Carboniferous.

A-type granites have been the subject of considerable interest due to their distinct anorogenic geological background. The A-type and arc-related granites are crucial in deciphering the evolution of the ocean closure and continental collision in the Tibet Plateau. The demise of the Bangong–Nujiang suture zone (BNSZ) and the Yarlung–Tsangpo suture zone was accompanied by the emplacement of volumes of syn-collisional and post-collisional granites. Controversy has persisted regarding the contribution of the collisional granites within the Lhasa Block to the growth of the Tibetan Plateau. This study provides key evidence about the evolution of the Lhasa Block and Bangong–Nujiang Ocean (BNO) by the newly documented 1200 km long, Early Cretaceous A-type acidic magmatic belt. The resolution was achieved through the utilization of petrology, whole-rock geochemistry, zircon U-Pb geochronology, and in situ zircon Hf isotope analysis of the Burshulaling Granites in the eastern segment and previous existing data in the central and western segment of the Lhasa Block. The Burshulaling Granites are characterized as peraluminous, high-K calc-alkaline series, indicating a post-collision setting with high temperature and low pressure. The zircon grains from two granite samples yield 206Pb/238U ages of 115–113 Ma. In situ zircon Hf analyses with 206Pb/238U ages give εHf(t) of −6.2–0.6, showing prominent characteristics of crust-mantle interaction. Granites from east to west exhibit whole-rock geochemical and geochronological similarities that fall within the well-constrained Early Cretaceous time frame (117–103 Ma) and track post-collisional A-type acidic magmatic belt along BNSZ. We argue that this magmatism resulted from slab break-off or orogenic root detachment, leading to melting and mixing of the lower crust. Meanwhile, this study indicates the existence of the Bangong–Nujiang Ocean southward subduction or a collapse following an Andean-type orogen.

The mature flesh of Cornus officinalis exhibits a vibrant red color, attributed to its rich anthocyanin content, imparting significant edible and medicinal value. Vibrant colors not only enhance the visual allure of medicinal materials but also maintain a close association with their intrinsic quality. However, the intricate process of pigment formation governing the anthocyanin accumulation in the pericarp of Cornus officinalis remains poorly understood. In this study, we conducted the comprehensive sampling and analysis of pericarp tissues at three distinct developmental stages, employing morphological-structure observation and metabolomic and transcriptomic techniques. Our findings reveal a substantial increase in the anthocyanin accumulation during the transition to the red stage of Cornus officinalis fruit maturation. Metabolomic profiling identified the highest expression levels of Cyanidin-3-O-glucoside and Pelargonidin-3-O-rutinoside during the mature stage, suggesting their association with the red coloration of the fruit. Through RNA sequencing, we identified 25,740 differentially expressed genes (DEGs), including 41 DEGs associated with anthocyanin biosynthesis. The correlation between the DEG expression levels and anthocyanin content was explored, further elucidating the regulatory network. Additionally, we validated the pivotal role of the candidate gene BZ1 in the synthesis of Cyanidin-3-O-glucoside through qRT-PCR, confirming its crucial impact on anthocyanin accumulation. This study provides preliminary insights into anthocyanin accumulation in Cornus officinalis, laying the foundation for the future development of new cultivars with enhanced anthocyanin contents.

A cooperative non-orthogonal multiple access (NOMA) system was proposed to support unicast primary user and multiple multicast services based on multiple relays strategy.Under the Rayleigh channel, the secondary user with the best channel condition from each multicast group was selected as full-duplex relay to decode and forward the unicast primary user’s signal, and the primary user employed the maximum ratio combining (MRC) technique to improve the signal to interference and noise ratio (SINR).The closed-form expressions for the outage probability of primary user in full-duplex and half-duplex modes with multi-relay simultaneous forwarding (MRSF) and optimal relay forwarding (ORF) were derived and verified by Monte Carlo simulations.The results verify that full-duplex relay outperforms half-duplex relay scheme.Furthermore, with same number of multicast groups, the MRSF strategy effectively improve the unicast primary user outage performance, in comparison with ORF strategy, when the number of multicast groups increases, the improvement becomes more significant.

Objective The classification and clinical usage of the different species of bead ginseng are often confused. Therefore, we conducted an integrated metabolomics and transcriptome analysis of three main species of Panax, including Panax japonicas, Panax pseudoginseng, and Panax pseudo-ginseng var. elegantior. Methods A broad metabolome and transcriptome analysis for three origins of bead ginseng plants was performed using UPLC-ESI-MS/MS, RNA sequencing and annotation, and bioinformatic analysis of transcriptome data. Results The levels of 830 metabolites were determined. A total of 291 differentially accumulated metabolites (DAMs) between Panax pseudo-ginseng var. elegantior and Panax japonicas (Group A), with 73 upregulated and 218 downregulated. A total of 331 DAMs (110 upregulated and 221 downregulated) were found between Panax pseudoginseng and Panax japonicas (group B). There were 160 DAMs (102 up-regulated and 58 down-regulated) between Panax pseudoginseng and Panax pseudo-ginseng var. elegantior (group C). In addition, RNA sequencing was performed in the above three ways. A total of 16,074 differential expression genes (DEGs) were detected between Group A, in which 7,723 genes were upregulated and 8,351 genes were downregulated by RNA sequencing. Similarly, 15,705 genes were differentially expressed between group B, in which 7,436 genes were upregulated and 8,269 genes were downregulated. However, only 1,294 genes were differentially expressed between group C, in which 531 genes were upregulated and 763 genes were downregulated. We performed differential gene analysis on three groups of samples according to the Venn diagram and found that 181 differential genes were present. A total of 3,698 and 2,834 unique genes were in groups A and B, while 130 unique genes were in group C. Conclusions This study provides metabolome and transcriptome information for three bead ginseng plants. The analysis of the metabolite content showed differences in the attributes of the three bead ginseng, contained mainly flavonoids, phenolic acids as well as terpenes.

Abstract Background Perineural invasion (PNI) is a typical pathological characteristic of salivary adenoid cystic carcinoma (SACC) and other neurotrophic cancers. The mechanism of the neural microenvironment controlling tumor progression during the PNI process is unclear. In the present study, we investigated the role and molecular mechanisms of nerve‐derived neuropeptide galanin (GAL) and its receptor (GALR2) in the regulation of PNI in SACC. Methods Immunohistochemistry staining and clinical association studies were performed to analyze the expression of GAL and GALR2 in SACC tissues and their clinical value. Dorsal root ganglion or SH‐SY5Y cells were co‐cultured with SACC cells in vitro to simulate the interactions between the neural microenvironment and tumor cells, and a series of assays including transcriptome sequencing, Western blot, and Transwell were performed to investigate the role and molecular mechanism of GAL and GALR2 in the regulation of SACC cells. Moreover, both the in vitro and in vivo PNI models were established to assess the potential PNI‐specific therapeutic effects by blocking the GAL/GALR2 axis. Results GAL and GALR2 were highly expressed in SACC tissues, and were associated with PNI and poor prognosis in SACC patients (p

Abstract Device‐to‐device (D2D) and full duplex (FD) technologies demonstrate immense potentials to improve the spectral efficiency of wireless networks. However, their synergistic combination to reap added benefits is proved to be technically challenging. This letter investigates the throughput‐maximization resource allocation problem for FD D2D communications underlaying cellular networks. The problem is decoupled into two subproblems, namely power allocation and channel assignment, which are solved by using a novel quadratic transform based scheme and the Kuhn–Munkres algorithm, respectively. Simulation results show that the proposed algorithm outperforms existing ones in terms of overall system throughput.

The social domain was introduced to multi-hop D2D (device-to-device) communication in cellular network scenarios, and a novel relay selection algorithm for multi-hop D2D communication under cellular network was proposed.Unlike existing relay selection algorithms, the proposed algorithm selects relays for each hop in reverse order, which reduces the signaling overhead caused by algorithm implement.Then, social domain information of mobile terminals was introduced to the algorithm and its influence on the algorithm’s performance was studied, which was found significant enough not to be overlooked hence providing useful guidance to designing algorithms in practical systems.Moreover, via extensive Monte Carlo simulations, it is discovered that the proposed algorithm outperforms the benchmarks in terms of data throughput and energy efficiency in absence of social relationship information.In a more practical implementation with social relationship information included, the proposed algorithm though naturally achieving less throughput, significantly outperforms the benchmarks in energy efficiency.

ObjectiveThe purpose of this study is to establish model for assessing inert nodules predicting nodule volume-doubling.MethodsA total of 201 patients with T1 lung adenocarcinoma were analysed retrospectively pulmonary nodule information was predicted by an AI pulmonary nodule auxiliary diagnosis system. The nodules were classified into two groups: inert nodules (volume-doubling time (VDT)>600 days n=152) noninert nodules (VDT>(INM) volume-doubling time estimation model (VDTM) were constructed based on a deep learning-based neural network. The performance of the INM was evaluated by the area under the curve (AUC) obtained from receiver operating characteristic (ROC) analysis the performance of the VDTM was evaluated by R2(determination coefficient).ResultsThe accuracy of the INM in the training and testing cohorts was 81.13% and 77.50%, respectively. The AUC of the INM in the training and testing cohorts was 0.7707 (95% CI 0.6779-0.8636) and 0.7700 (95% CI 0.5988-0.9412), respectively. The INM was effective in identifying inert pulmonary nodules; additionally, the R2 of the VDTM in the training cohort was 0.8008, and that in the testing cohort was 0.6268. The VDTM showed moderate performance in estimating the VDT, which can provide some reference during a patients’ first examination and consultationConclusionThe INM and the VDTM based on deep learning can help radiologists and clinicians distinguish among inert nodules and predict the nodule volume-doubling time to accurately treat patients with pulmonary nodules.

Abstract Background Few models about the personalized prognosis evaluation of buccal mucosa cancer (BMC) patients were reported. We aimed to establish predictive models to forecast the prognosis of BMC patients. Methods The complete clinicopathological information of BMC patients from the surveillance, epidemiology and end results program was collected and reviewed retrospectively. Two nomograms were established and validated to predict long-term overall survival (OS) and cancer-specific survival (CSS) of BMC patients based on multivariate Cox regression survival analysis. Results 1155 patients were included. 693 and 462 patients were distributed into modeling and validation groups with 6:4 split-ratio via a random split-sample method. Based on the survival analysis, independent prognostic risk factors (variables that can be used to estimate disease recovery and relapse chance) influencing OS and CSS were obtained to establish nomograms. Then, we divided the modeling group into high- and low-risk cohorts. The low-risk cohort had improved OS and CSS compared to the high-risk cohort, which was statistically significant after the Log-rank test (p

Abstract Numerous studies have shown that long noncoding RNAs (LncRNAs) are involved in the development and immune escape of head and neck squamous-cell carcinoma (HNSCC). However, the specific regulatory mechanisms by which LINC01123 regulates HNSCC and its correlation with immunity remain unclear. Therefore, this study’s primary purpose was to explore the mechanisms by which LINC01123 regulates the immune escape and progression of HNSCC. This study confirmed that LINC01123 is competitively bound to miR-214-3p, and miR-214-3p specifically targets B7–H3. The effects of LINC01123, B7–H3, and miR-214-3p on tumor progression, CD8+T-cell-mediated immune response, and the tumorigenicity of HNSCC in vitro and in vivo were examined through the downregulation or upregulation of LINC01123, B7–H3, and miR-214-3p. Our results indicated that LINC01123 and B7–H3 were highly expressed in HNSCC and are associated with poor prognosis in patients. Notably, overexpression of LINC01123 or B7–H3 or downregulation of miR-214-3p inhibited the function of CD8+T cells and promoted the progression of HNSCC. Therefore, LINC01123 acts as a miR-214-3p sponge to inhibit the activation of CD8+T cells and promote the progression of HNSCC by upregulating B7–H3.

Background/ObjectiveThe third-generation epidermal growth factor receptor (EGFR) -tyrosine kinase inhibitor (TKIs), such as osimertinib, designed for targeting the acquired drug-resistant mutation of EGFR T790M, was approved as the first-line therapy for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Thus, detection of the EGFR T790M mutation for NSCLC is crucial. However, tissue samples are often difficult to obtain, especially in patients at advanced stages. This study assessed the performances of droplet digital polymerase chain reaction (ddPCR) and next-generation sequencing (NGS) in detecting EGFR T790M status and abundance in the plasma ctDNA samples of patients with NSCLC. We also explored the association between T790M status and abundance and the response to third-generation EGFR-TKIs.MethodsA total of 201 plasma samples with matched tissues, 821 plasma samples, and 56 patients who received third-generation EGFR-TKIs with response evaluation were included in this study. ddPCR and NGS were used to detect the mutation status and abundance of T790M in the tissues and/or blood samples.ResultsThe results showed that the sensitivity and the specificity of EGFR T790M mutation status detected by ddPCR in plasma samples were 81.82% and 91.85%, respectively, compared with the tissue samples, with a consistency coefficient of 0.740. Among the 821 plasma samples, the positive rates of EGFR T790M detected by ddPCR and NGS were 34.2% (281/821) and 22.5% (185/821), respectively. With NGS results as the reference, the sensitivity and the specificity of ddPCR were 100% and 84.91%, respectively, and the consistency coefficient of the two methods was 0.717. In addition, we found that a higher EGFR T790M abundance was linked to a higher treatment response rate to the third-generation EGFR-TKIs regardless of the classification of the median value of 0.43% (P = 0.016) or average value of 3.16% (P = 0.010).ConclusionTaking these data together, this study reveals that ddPCR is an alternatively potent method for the detection of EGFR T790M in the plasma samples of NSCLC patients.

Abstract Glioblastoma (GBM) is a strikingly heterogeneous and lethal brain tumor with very poor prognosis. LncRNAs play critical roles in the tumorigenesis of GBM through regulation of various cancer-related genes and signaling pathways. Here, we focused on the essential role of EMT and identified 78 upregulated EMT-related genes in GBM through differential expression analysis and Gene set enrichment analysis (GSEA). A total of 301 EMT-related lncRNAs were confirmed in GBM through Spearman correlation analysis and a prognostic signature consisting of seven EMT-related lncRNAs (AC012615.1, H19, LINC00609, LINC00634, POM121L9P, SNHG11, and USP32P3) was established by univariate and multivariate Cox regression analyses. Significantly, Kaplan–Meier analysis and receiver-operating-characteristic (ROC) curve validated the accuracy and efficiency of the signature to be satisfactory. Quantitative real-time (qRT)-PCR assay demonstrated the expression alterations of the seven lncRNAs between normal glial and glioma cell lines. Functional enrichment analysis revealed multiple EMT and metastasis-related pathways were associated with the EMT-related lncRNA prognostic signature. In addition, we observed the degree of immune cell infiltration and immune responses were significantly increased in high-risk subgroup compared with low-risk subgroup. In conclusion, we established an effective and robust EMT-related lncRNA signature which was expected to predict the prognosis and immunotherapy response for GBM patients.

Objectives: In head and neck squamous cell carcinoma (HNSCC), the interaction between epithelial-mesenchymal transformation (EMT) and hypoxia has been confirmed, and corresponding treatment methods have been investigated. Few studies have examined its combined effects and its potential clinical use, however. As a result, we developed a new scoring system based on EMT and hypoxia.Methods: We combined 200 hypoxia-related genes with 1184 EMT-related genes and finally constructed a score risk model containing 14 characteristic factors named the comprehensive index of EMT and hypoxia (CIEH) by the Lasso-Cox regression and univariate Cox regression method, which is used to predict prognosis and to guide treatment planning in HNSCC patients. Furthermore, we examined HNSCC expression of CIEH-related genes using the human protein atlas database.Results: Based on survival analysis results, CIEH value had a high prognostic value in HNSCC patients, a high CIEH value carries a poor prognostic significance in HNSCC. It is noteworthy that the CIEH value was correlated with tumor immune infiltration. Moreover, the CIEH had significant differences in age, stage, N, laterality, and peripheral nerve invasion, and that the CIEH could be an independent prognostic factor.Conclusions: This study constructed a CIEH model containing 14 characteristic factors, including hypoxia-related genes and EMT genes, that may be able to serve as potential biomarkers for HNSCC. According to the 14 characteristic factors in the CIEH model, a diagnostic kit can be packaged in the future to evaluate the survival of patients before tumor surgery and guide the subsequent treatment plan.

Background and objective Targeted therapy for patients with driver genes positive and immunotherapy for patients with driver gene-negative but high programmed death ligand 1 (PD-L1) expression are the standards of first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). The treatment options for patients with driver gene positive and high PD-L1 expression are still worth exploring. Methods The characteristics of 315 patients with NSCLC were identified to analyze the clinicopathological characteristics of patients with driver gene positive and high PD-L1 expression, and the efficacy of targeted therapy. Results Among the 315 patients, the total positive rate of driver genes was 62.2%, and the high PD-L1 expression rate (≥50.0%) was 11.2%. The proportion of patients with driver gene positive and high PD-L1 expression was 10.7%. PD-L1 was highly expressed in patients with epidermal growth factor receptor (EGFR) mutation, KRAS mutation, ALK fusion, BRAF mutation, and MET 14 exon skip mutation, the proportions were 7.8% (11/141), 18.2% (4/22), and 23.1%, (3/13), 50.0% (2/4) and 100.0% (1/1) respectively. EGFR mutation positive with PD-L1 high expression was mainly in patients with stage IV lung adenocarcinoma. KRAS mutation positive with PD-L1 high expression was mainly in patients with a history of smoking. Among them, two patients were followed in detail for targeted therapy, who with ALK fusion-positive and PD-L1 high expression (90.0%), EGFR L858R mutation and PD-L1 high expression (70.0%) respectively. The total OS of the patients was 5 months, 2 months. Conclusion The high PD-L1 expression rate in NSCLC patients with different driver gene mutations was variable, which maybe correlated with distinct clinicopathological characteristics. Patients with sensitive mutations and high PD-L1 expression may be less benefit from targeted therapy and have poor prognosis.

Background and objective New treatment methods such as targeted therapy and immune checkpoint inhibitors have been applied to lung cancer patients. It is necessary to further understand the patients with lung cancer combined with pulmonary tuberculosis with the development of lung cancer research. The purpose of this study was to analyze the clinical characteristics of lung cancer patients with pulmonary tuberculosis, the status of driver genes, and their relationships. Methods A retrospective analysis was performed on 405 patients with lung cancer and pulmonary tuberculosis hospitalized in our hospital from January 2014 to December 2019. The relationship between clinical characteristics and driver genes status was analyzed. Results Among the 405 patients with lung cancer combined with pulmonary tuberculosis, 77.3% were male and 85.3% were patients with a history of smoking. The pathological type was mainly lung adenocarcinoma. When there were cavities in chest computed tomography (CT) , squamous cell carcinoma was the main type. 214 patients underwent driver genes testing. The epidermal growth factor receptor (EGFR) gene mutation rate was 35.9%, of which 41.8% were exon 19 deletion mutations and 50.9% were exon 21 L858R mutations. When there were cavities in the chest CT, the EGFR mutation rate was significantly reduced (16.1%). The positive rate of anaplastic lymphoma kinase (ALK) fusion gene detection was 2.5%, the mutation rate of c-ros oncogene 1 receptor kinase (ROS1) gene was 1.9%, the mutation rate of V-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene was 1.1%, and the mutation rate of Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene was 10.1%. The genetic mutation rate of female patients with lung cancer and pulmonary tuberculosis was 50.0%, and that of men was 27.9%. Conclusion Patients with lung cancer and pulmonary tuberculosis are predominantly male with smoking history. Adenocarcinoma is the most common pathological type. The positive rate of gene mutation was not significantly different from that of simple lung cancer, but when there were cavities in the chest image, the genetic mutation rate was significantly reduced.

Background and objective The patients with advanced lung adenocarcinoma should select targeted drugs based on the type of tumor epidermal growth factor receptor (EGFR) gene mutation. However, it is difficult to collect tumor tissue of advanced lung adenocarcinoma, and some experts agree that peripheral blood can be used as a substitute for tumor tissue as a test specimen. This paper aimed to investigate the clinical value of ddPCR and super-amplification refractory mutation system (ARMS) in detecting EGFR gene mutation in peripheral blood of patients with advanced lung adenocarcinoma. Methods A total of 119 patients diagnosed in Beijing Chest Hospital Affiliated to Capital Medical University from February 2016 to February 2019 were collected, and the sensitivity and specificity of plasma ctDNA EGFR gene mutation detected by ddPCR and super-arms were compared. Some patients with positive EGFR gene mutations received oral treatment with first-line EGFR tyrosine kinase inhibitors (EGFR-TKI). The patients were divided into subgroups according to the test results. In group 1, both ddPCR and super-arms showed positive EGFR gene mutation results, with 21 cases. In group 2, ddPCR and super-arms detection of EGFR gene mutation were all negative, with 16 cases. In group 3, the ddPCR test was positive and the super-arms test was negative, with 5 cases. In group 4, the ddPCR test result was negative while the super-arms test result was positive. Since the number of patients in group 4 was 0, no statistics were included. Objective response rate (ORR) and disease control rate (DCR) were used to evaluate the short-term outcome, and progression-free survival (PFS) was compared with survival analysis to evaluate the long-term outcome. Results EGFR mutations were detected in 58 (48.7%) of 119 patients with advanced lung adenocarcinoma. The coincidence rate between ddPCR and EGFR gene mutation in tumor tissues was 82.4% (Kappa=0.647, P0.05). Survival analysis showed that the PFS of the three groups was compared. The difference was not statistically significant (χ2=2.221, P=0.329). Conclusion ddPCR, as a high sensitivity and specificity liquid gene detection method, can be used as a reliable method to detect the mutation of plasma ctDNA EGFR gene in patients with advanced lung adenocarcinoma. The results of plasma genetic testing can also be used as the basis for predicting the efficacy of EGFR-TKIs in patients.

The roots of Salvia miltiorrhiza Bunge. are commonly used in the treatment of cardiovascular diseases, and tanshinones and salvianolic acids are its main active ingredients. However, the composition and content of active ingredients of S. miltiorrhiza planted in different regions of the soil environment are also quite different, which adds new difficulties to the large-scale and standardization of artificial cultivation. Therefore, in this study, we measured the active ingredients in the roots of S. miltiorrhiza and the contents of rhizosphere soil elements from 25 production areas in eight provinces in China, and used the data to develop a prediction model based on BP (back propagation) neural network. The results showed that the active ingredients had different degrees of correlation with soil macronutrients and trace elements, the prediction model had the best performance (MSE = 0.0203, 0.0164; R2 = 0.93, 0.94). The artificial neural network model was shown to be a method that can be used to screen the suitable cultivation sites and proper fertilization. It can also be used to optimize the fertilizer application at specific sites. It also suggested that soil testing formula fertilization should be carried out for medicinal plants like S. miltiorrhiza, which is grown in multiple origins, rather than promoting the use of “special fertilizer” on a large scale. Therefore, the model is helpful for efficient, rational, and scientific guidance of fertilization management in the cultivation of S. miltiorrhiza.

The application of cooperative multicast in a non-orthogonal multiple access (NOMA) system and its performances was studied where a mixed service scenario consisting of a number of the multicast users and one unicast user was employed.In such a system,a cooperative relay path selection strategy was used and a best channel conditioned multicast user was selected as relay user to relay the unicast user’s signal.The unicast user outage probability and the relay user’s capacity in closed-form were then derived.Mont Carlo simulation results validate the analysis and show that the proposed scheme significantly enhances outage probability for unicast user while maintaining the same ergodic capacity for the relay user.

This paper investigates the resource allocation problem in device-to-device (D2D) communications underlaying a non-orthogonal multiple access (NOMA)-based cellular network with energy harvesting, where the energy harvesting-powered D2D communications share the downlink resources of the cellular network. To fully exploit the high-data-rate D2D links in this system, a two-phase framework is proposed for D2D users. In particular, the D2D users harvest energy from the base station (BS) in the first phase and then transmit their own information using the harvested energy in the second one. Meanwhile, the D2D communications could cause severe interference to cellular users (CUs) and hence probably ruin the SIC decoding order of the CUs. To deal with this issue, joint power allocation and time scheduling scheme is proposed to maximize the throughput of the D2D links while guaranteeing the quality of service (QoS) for each CU. Through rigorous derivation, the optimal power control and time scheduling parameters are analyzed to simplify the optimization problem formulation. The closed-form optimal solution is derived in some cases. In other cases, a gradient-based algorithm is employed to find an appropriate sub-optimal solution. The simulation results are demonstrated to validate the superiority of the proposed scheme over the conventional orthogonal multiple access (OMA) scheme.

PurposeCirculating cell-free DNA (cfDNA) level has been demonstrated to be associated with efficacy in first generation EGFR TKIs in non-small cell lung cancer (NSCLC). However, the role of dynamic cfDNA analysis using next-generation sequencing (NGS) in patients with subsequent third-generation EGFR TKIs remains unclear.MethodsFrom 2016 to 2019, 81 NSCLC patients with EGFR T790M mutation either in tissue or plasma who received third-generation EGFR TKIs treatment were enrolled. CfDNA were sequenced by NGS with a 425-gene panel. The association of clinical characteristics, pretreatment, dynamic cfDNA and T790M level with outcomes in patients treated with the third-generation TKIs were analyzed.ResultsIn univariate analysis, the median PFS of patients with undetectable cfDNA level during treatment was significantly longer than those with detectable cfDNA (16.97 vs. 6.10 months; HR 0.2109; P < 0.0001). The median PFS of patients with undetectable T790M level during treatment was significantly longer than those with detectable T790M (14.1 vs. 4.4 months; HR 0.2192; P < 0.001). Cox hazard proportion model showed that cfDNA clearance was an independent predictor for longer PFS (HR 0.3085; P < 0.001) and longer OS (HR 0.499; P = 0.034). The most common resistant mutations of the third-generation TKIs were EGFR C797S (24%). CDK6 CNV, GRIN2A, BRCA2, EGFR D761N, EGFR Q791H, EGFR V843I, and ERBB4 mutation genes may possibly be new resistant mechanisms.ConclusionsPatients with undetectable cfDNA during the third-generation EGFR TKI treatment have superior clinical outcomes, and dynamic cfDNA analysis by NGS is valuable to explore potential resistant mechanisms.

HER2 mutations have emerged as oncogenic driver gene mutations in non-small cell lung cancer (NSCLC), which have not been described in detail like other driver gene mutations. Here, 295 patients with advanced lung adenocarcinoma were retrospectively screened for HER2 mutations using next-generation sequencing (NGS), and the positive cases were validated by Sanger sequencing. We identified five cases with HER2 exon 20 insertions, representing 1.7% of 295 lung adenocarcinomas. Among them, four different subtypes of HER2 exon 20 insertions were identified, including a rare subtype G778_S779insCPG never reported before with a partial response (PR) to pyrotinib and progression-free survival (PFS) of 12.8 months. Our findings reveal that HER2 exon 20 insertion mutations were detected in a small subset of lung adenocarcinomas. Given the different drug sensitivities, determining the mutation subtype by next-generation sequencing at the time of diagnosis might make sense.

A mechanically-activated chemoselective Heck coupling for the synthesis of 3-vinylindazoles has been developed with the aid of catalytic amounts of TBAB and NaBr as both dehalogenation restrainer and grinding auxiliary. After tuning of the chemical conditions and mechanical parameters, a series of non-activated 3-bromoindazoles and a broad scope of olefins worked well to give the corresponding coupling products in good to excellent yields. A further application of this protocol was performed in a two-step mechanochemical Heck/Migita cross coupling, which provided a highly efficient route for the synthesis of axitinib.

Background and objective Non-small cell lung cancer (NSCLC) has been transformed from the treatment according to histological type to genotype treatment model. The epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genes are the most important drivers in lung cancer. The aim of this study is to explore the clinical characteristics and prognostic factors of patients with advanced NSCLC with different genotypes. Methods We retrospectively reviewed the clinical data of 553 advanced NSCLC patients with EGFR mutations and ALK positive who were hospitalized in the Beijing Chest Hospital from July 2004 to December 2015, and the independent prognostic factors of patients were analyzed by Cox proportional hazards regression model. Results The clinical data of 553 patients (227 with EGFR mutations, 58 with ALK positive, 2 with EGFR and ALK co-mutation and 266 with wild-type) with advanced NSCLC were enrolled in this study. The median survival time of 227 patients with EGFR mutations was 28.7 mo (95%CI: 22.160-35.240), and the performance status (PS) score (0-1) (HR=4.451; 95%CI: 2.112-9.382; P

Objective: The present study investigated the roles and underlying mechanism of CCL2/CCR2 axis in the interactions between tumor cells and tumor-associated macrophages (TAMs) during the progression of salivary adenoid cystic carcinoma (SACC).Methods: Immunohistochemical staining and survival analysis were performed to study the correlation and clinical value of CD68, CD163, CCL2, and CCR2 expression in SACC cases. CCL2 silencing by RNA interference and CCR2 blocking by CCR2 specific antagonist (RS504393) were performed. ELISA, qRT-PCR, western blot, immunofluorescence, flow cytometry, CCK8, scratch wound healing, and transwell assays were used to explore the functional roles and possible mechanism of CCL2/CCR2 axis in the interactions between SACC cells and TAMs. The effects of targeting TAMs by blocking the CCL2/CCR2 axis were investigated in a xenograft mice model with SACC cells.Results: The high infiltration of TAMs marked by CD68 and high infiltration of M2 TAMs marked by CD163 were significantly correlated with the expression of CCL2 and CCR2 in SACC tissues. Notably, the high infiltration of TAMs and the overexpression of CCL2 were obviously associated with the clinical progression and poor prognosis of SACC. SACC cells derived CCL2 could activate its receptor CCR2 expression in TAMs in vitro. The in vitro results further indicated that the SACC cells derived CCL2 was involved in the recruitment, M2 polarization, and GDNF expression of TAMs through the CCL2/CCR2 axis. Meanwhile, TAMs derived GDNF promoted the proliferation, migration, and invasion of SACC cells through the GDNF/p-RET pathway. Treating immunodeficient mice with the CCR2 antagonist (RS504393) greatly inhibited the infiltration of TAMs and the tumorigenicity of SACC cells.Conclusion: These new findings indicated that the CCL2/CCR2 axis promoted the progression of SACC cells via recruiting and reprogramming TAMs. Targeting TAMs by blocking the CCL2/CCR2 axis might be a prospective strategy for SACC therapy.

Background and objective Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) is an important subtype of lung cancer. The standard modality of ALK-positive NSCLC with brain metastases remains uncertain. Methods We collected data on clinical characteristics and treatment of patients with ALK-positive NSCLC and brain metastases between March 2013 and March 2016 and retrospectively analyzed patient outcomes. Results In 84 ALK-positive patients with advanced NSCLC, 22 (26.2%) had brain metastases during the initial diagnosis of lung cancer, among which 3 patients with EGFR mutation were excluded, and 19 patients were analyzed. Median intracranial progression-free survival (PFS) was 12.0 months. PFS for patients who received first-line local brain therapy (P=0.021) and crizotinib therapy (P=0.030) was superior to PFS for patients without such therapies. PFS for patients who received first-line crizotinib combined with local brain therapy was 27.0 months and only 4.2 months for those who received crizotinib alone. Conclusion First-line crizotinib therapy combined with local brain treatment can improve intracranial PFS for ALK-positive NSCLC with brain metastases. This finding should be confirmed further through multicenter, prospective clinical trials with large sample size.

Background and objective Kirsten rat sarcoma viral oncogene (KRAS) mutation is one of the major driver genes of non-small cell lung cancer (NSCLC). KRAS is a resistant predictor of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), which raises controversy because of its role in chemotherapy sensitivity and prognosis. The aim of this study is to accumulate clinical experience in treating NSCLC patients harboring KRAS mutation. Methods A total of 107 NSCLC patients harboring KRAS mutation were analyzed retrospectively. The efficacy was analyzed in terms of first-line chemotherapy or EGFR-TKIs therapy. Results The objective response rate (ORR) to first-line chemotherapy of 52 patients with advanced disease harboring KRAS mutation was 9.6%. The disease control rate (DCR) was 53.8%, and the median progression-free survival (PFS) was 3 months. The ORR to EGFR-TKIs therapy in 21 patients harboring KRAS mutation and EGFR/KRAS co-mutation was 9.5%; the DCR was 23.8%, and the median PFS was 1 month. The ORR and DCR to EGFR-TKIs therapy of patients with EGFR/KRAS co-mutation were significantly higher than those of patients with KRAS mutation (50% vs 0, P=0.029; 75% vs 11.8%, P=0.043); the median PFS was also significantly longer (3 months vs 1 month, P=0.004). Conclusion The efficacy to first-line chemotherapy and EGFR-TKIs therapy in NSCLC patients harboring KRAS mutation was poor; thus, new drugs should be developed. Furthermore, the existence of EGFR/KRAS co-mutation was confirmed. Hence, EGFR-TKIs therapy should be administered to patients with EGFR/KRAS co-mutation.

Background and objective Mutations in epidermal growth factor receptor (EGFR) and KRAS are important markers in non-small cell lung cancer, which are closely related to the clinical therapeutic effect. To analysis the EGFR and KRAS gene mutation rate and its relationship with clinical features in patients with lung adenocarcinoma. Methods 395 patients with treatment naïve lung adenocarcinoma, tumor tissue samples were available for testing. Tumor sample EGFR and KRAS mutation status were detected using mutant enriched liquidchip. Results 395 cases of lung adenocarcinoma, EGFR mutations were detected in 192 cases (48.9%), KRAS mutations were detected in 29 cases (7.8%), and the presence of EGFR and KRAS mutation were detected in 1 case (0.3%). EGFR mutations were found to occur significantly more often in female than in male patients (62.0% vs 37.1%, P0.05) in each clinical factors, only occurred in the wild type EGFR gene in patients (13.5%, 27/200) was significantly higher than that of patients with EGFR mutation (1.0%, 2/192), the difference was statistically significant (P

Background and objective Activating mutations in epidermal growth factor receptor (EGFR) and KRAS are important markers in non-small cell lung cancer. However, EGFR and KRAS gene mutations in lung squamous cell carcinoma are rarely reported. The aim of this study was to analyze EGFR and KRAS gene mutation rate and their relationship with clinical features in patients with lung squamous cell carcinomas. Methods A total of 139 patients undergoing treatment for naïve lung squamous cell carcinomas with tumor tissue samples available for testing were recruited. EGFR and KRAS mutation statuses of the tumor samples were detected using a mutant enriched liquid chip. Results Of the 139 cases of lung squamous cell carcinoma, EGFR mutations were detected in 25 cases (18%), KRAS mutations were detected in 7 cases (5%), and the presence of both EGFR and KRAS mutations was detected in 1 case (0.7%). EGFR mutations occurred more often in females than in males (33.3% vs 16.5%) and in patients that never smoked than in those who smoke (29.6% vs 16.1%). However, the difference did not reach statistical significance (P>0.05). No significant differences were observed in age, stage, and different biopsy type. KRAS mutations occurred more often in males than in females (5.5% vs 0%), but the difference did not reach statistical significance (P>0.05). No significant differences were observed in age, stage, different biopsy type, and smoking status (P>0.05). Conclusion EGFR and KRAS mutations were low in lung squamous cell carcinomas, and had no significant correlation with clinical features. Before using tyrosine kinase inhibitor targeted therapy, EGFR and KRAS mutations should be detected in patients with lung squamous cell carcinomas.

Two new furostanol saponins 1–2 and a new spirostanol saponin 3 were isolated together with two known furostanol saponins 4–5 from the roots and rhizomes of Tupistra chinensis. Their structures were characterized as 1β,2β,3β,4β,5β,26-hexahydroxyfurost-20(22), 25(27)-dien-5,26-O-β-d-glucopyranoside (1), 1β,2β,3β,4β,5β,6β,7α,23ξ,26-nona-hydroxyfurost- 20(22),25(27)-dien-26-O-β-d-glucopyranoside (2), (20S,22R)-spirost-25 (27)-en-1β,3β,5β- trihydroxy-1-O-β-d-xyloside (3), tupisteroide B (4) and 5β-furost-Δ25(27)-en-1β,2β,3β,4β,5β,7α, 22ξ,26-octahydroxy-6-one-26-O-β-d-glucopyranoside (5), respectively, by extensive use of spectroscopic techniques and chemical evidence. Additionally, the in vitro cytotoxic activity of 1–4 was evaluated on human A549 and H1299 tumor cell lines, and compound 3 exhibited cytotoxicity against A549 cells (IC50 86.63 ± 2.33 μmol·L−1) and H1299 cells (IC50 88.21 ± 1.34 μmol·L−1).

Background and objective Status of epidermal growth factor receptor (EGFR) gene is a predictor of response to EGFR tyrosine kinase inhibitor (TKI). However, little is know about the relationship between EGFR status and response to chemotherapy. We evaluated the prediction value of EGFR mutation status on response to first-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods The data of 181 patients with stage IIIb/IV NSCLC who diagnosed by histopathology from January 10, 2006 to December 20, 2013 in Beijing Chest Hospital, Capital Medical University were collected. The relationships between EGFR gene status, clinical characteristics and response and progression-free survival (PFS) were analyzed. Results All of the 181 patients’ EGFR statuses were determined. 75 (41.4%) patients harbored EGFR-activating mutations and 106 (58.6%) patients were EGFR wild-type. All patients received first-line chemotherapy. The objective response rate (ORR) was 26.0% and disease control rate (DCR) was 70.2%. Patients with EGFR-activating mutations had a higher DCR than patients with EGFR wild-type (84.0% vs 60.4%, P=0.001) did. Subgroup analysis showed that the ORR and DCR in patients with EGFR exon 19 deletions were remarkably higher than those with EGFR wild-type (P = 0.049, 0.002, respectively). The DCR in patients with EGFR exon 21 L858R mutation was significantly higher than that in patients with EGFR wild-type (P=0.010). 168 patients were available for response evaluation in all of 181 patients and median PFS was 4.3 mo. The PFS of patients with adenocarcinoma was significantly higher than that patients with squamous cell carcinoma (4.7 mo vs 3.0 mo, P=0.036). The PFS in patients harbored EGFR-activating mutations was significantly higher than that in the patients with EGFR wild-type (6.3 mo vs 3.0 mo, P=0.002). The PFS of patients with a performance status (PS) of 0-1 was significantly higher than that in patients with a PS of 2 (4.4 months vs. 0.7 months, P= 0.016). Cox multivariate analysis indicates the EGFR-activating mutation is an independent factor affecting PFS (HR=0.654, 95%CI: 0.470-0.909, P=0.012). Conclusion EGFR-activating mutation is a predictor for PFS of first-line chemotherapy in advanced NSCLC patients.

Background and objective It has been proven that icotinib hydrochloride, as a molecule targeted drug, can be safely and efficiently used to treat advanced non-small cell lung cancer (NSCLC) for second-line or third-line. This research was aimed to investigate the efficacy and toxicity of icotinib hydrochloride as the first-line therapy for pulmonary adenocarcinoma. Results Among the 56 patients, the tumor objective response rate (ORR) and disease control rate (DCR) was 46.4% (26/56) and 78.6% (46/56), respectively. Among the 20 patients with EGFR analyses, 18 patients were positive for a mutation, ORR was 66.7% (12/18), DCR was 94.4% (17/18) respectively. The ORR with no history of smoke. EGFR positive mutation and appearance of rash were significantly higher than those with smoker, wild type EGFR, no information about EGFR and no appearance of rash (P

Background and objective Icotinib hydrochloride is the third single target EGFR-TKI used in clinical treatment of advanced non-small cell lung cancer (NSCLC). Clinical research reports on its efficacy and survival in patients with Recurrent Advanced NSCLC are still little.The aim of this study is to evaluate the efficacy and survival of Icotinib hydrochloride for patients with advanced non-small cell lung cancer who failed to previous chemotherapy and explore the association of clinical features with the efficacy and survival. Methods The clinical data of 60 NSCLC patients referred to the Beijing Chest Hospital, Capital Medical University from March 2009 to July 2012 were retrospectively analyzed. Results The overall response rate (ORR) was 45.0% and the disease control rate (DCR) was 80.0%. The median progression-free survival (PFS) time was 6.7 months. RR and PFS in female were superior to male (P=0.014, 0.013, respectively). RR, DCR in 2nd-line subgroup were superior to ≥3rd-line subgroup (P=0.020, 0.024, respectively). RR, DCR and PFS in EGFR mutation carriers were significantly superior to wild-type patients (P=0.006,

Background and objective Paclitaxel plus cisplatin (TP) is used as the standard regimen for patients with advanced non-small cell lung cancer (NSCLC). In this study, we compared the response rate (RR), overall survival (OS), and toxicity of the combined chemotherapy regimen of liposomal paclitaxel plus cisplatin (LP) with those of TP as first-line treatments for advanced NSCLC. Methods A total of 100 patients were randomly selected to be treated with liposomal paclitaxel or paclitaxel at a dose of 150 mg/m2 on day 1 plus cisplatin at a dose of 75 mg/m2 on days 1 and 2 per cycle every 21 days. Results All 100 patients were eligible. The median progression free survival was 5.1 months vs 4.2 months, the median OS was 9.0 months vs 9.3 months, and RR was 26% vs 24% in the LP and TP arms, respectively. No significant difference was observed (P=0.110, 0.342 and 0.890, respectively). There was no significant difference between grades 3 and 4 toxicity of the arms (P>0.05). Peripheral neuritis observed in the LP arm was significantly lower than that in the TP arm (8% vs 28%), and the difference was statistically significant (P=0.030). Conclusion The effects of LP and TP as first-line therapies for NSCLC are similar. However, peripheral neuritis in the LP arm is significantly lower than in the TP arm.

Background and objective Icotinib is the first self-developed small molecular drug in China for targeted therapy of lung cancer. Compared to the other two commercially available epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, icotinib is similar to them in chemical structure, mechanism of activity and therapeutic effects. To explore the efficacy and side effects of icotinib hydrochloride in the treatment of the advanced non-small cell lung cancer (NSCLC) patients with EGFR mutation and wild-type. Methods Patients with advanced NSCLC who were treated with icotinib hydrochloride in Beijing Chest Hospital were retrospective analyzed from March 2009 to December 2014. Results The clinical data of 124 patients (99 with EGFR mutation and 25 with wild type) with advanced NSCLC were enrolled in this study. The patients’ overall objective response rate (ORR) was 51.6 % and the disease control rate (DCR) was 79.8%; The patients with EGFR mutation, ORR was 63.6%, DCR was 93.9%. The ORR was 4.0% and the DCR was 24.0% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment in EGFR mutation patients was 10.5 months and 1.0 month in wild-type patients. The major adverse events were mild skin rash (30.6%) and diarrhea (16.1%). Conclusion Monotherapy with icotinib hydrochloride is effective and tolerable for the advanced NSCLC EGFR mutation patients.

Background and objective Serum tumor markers play important roles in diagnosis, response and prognosis monitoring for lung cancer. The clinical significance of serum level of tissue polypeptide specific antigen (TPS) was investigated in diagnosis, response monitoring and prognosis in patients with lung cancer, compared with carcinoembryonic antigen (CEA), precursor of gastrin-releasing peptide (Pro-GRP) and cytokeratin-19-fragments (CYFRA21-1). Methods Blood samples of eighty-two patients with lung cancer before treatment and some after chemotherapy were measured by ELISA for four tumor markers. Results Compared with lung benign diseases group and health control group, the positive rates and levels of TPS, CEA and Pro-GRP in patients with lung cancer were higher, with statistically significant difference. TPS in extensive-small cell lung cancer was significant higher than that in limited-small cell lung cancer. The positive rates and levels of TPS, CEA and Pro-GRP in patients after treatment had significant decreases compared with before treatment. TPS was an independent prognostic factor of non-small cell lung cancer. Conclusion TPS is valuable to diagnosis, response monitoring for patients with lung cancer, moreover, it maybe a useful factor of prognosis of non-small cell lung cancer.

Background and objective Results of studies on genetic polymorphisms of ERCC1 gene in DNA repair pathway which may affect response to platinum-based chemotherapy and survival in patients with non-small cell lung cancer are conflicting. The aim of this study is to prospectively assess the association between single nucleotide polymorphisms of C8092A and codon118 in ERCC1 and drug response in 90 patients with advanced non-small cell lung cancer treated with cisplatin-based chemotherapy. Methods All patients were treated with cisplatin-based chemotherapy. Genotypes of ERCC1 C8092A and codon118 were examined by sequencing, and the association between genotypes and response was evaluated. Results Genotype frequencies of ERCC1 C8092A were CC 40.0% (36/90), CA 48.9% (44/90) and AA 11.1% (10/90), frequencies of codon118 were CC 58.9% (53/90), CT 34.4% (31/90) and TT 6.7% (6/90). There was no significant difference in response rate of patients carrying with CC, compared with CA plus AA in C8092A (33.3% vs 29.6%, P=0.71). Response rate of patients carrying with CC in ERCC1 118 was 32.1%, 24.3% with CT plus CC (P=0.43). There was no difference in progression free survival between patients carrying with CC and CT plus TT in C8092A (5.2 months vs 5.4 months, P=0.62). There was no difference in progression free survival between patients carrying with CC and CA plus AA (5.5 months vs 5.3 months, P=0.59). Conclusion The results suggest that there is no association between polymorphisms in ERCC1 C8092A and codon118 and response in patients with advanced non-small cell lung cancer receiving cisplatin-based chemotherapy.

Four new steroidal constituents (1–4) along with two known steroidal glycosides (5 and 6) were isolated from the roots and rhizomes of Smilacina japonica. Analysis of their physicochemical properties and spectroscopic profiles identified the compounds as (25S)-5α-spirostan-9(11)-en-3β, 17α-diol (1); (25S)-5α-spirostan-9(11)-en-3β, 12β-diol (2); (25S)-5α-spirostan-9(11)-en-3β, 17α-diol-3-O-β-d-glucopyranoside (3); (25S)-5α-spirostan-9(11)-en-3β, 17α-diol-3-O-β-d-glucopyranosyl-(1→2)-[β-d-glucopyranosyl-(1→3)]-β-d-galactopyranoside (4); japonicoside B (5); and japonicoside C (6). All six compounds showed cytotoxic activity against SMMC-7712, Bel-7402, A549, H460, and K562 human cancer cells.

Background and objective Docetaxel is an active agent in the second-line treatment for non-small cell lung cancer (NSCLC), many clinical trials have demonstrated that it has similar efficacy to common first-line regimens for NSCLC. A randomized study was conducted to compare docetaxel plus cisplatin (DC) versus paclitaxel plus cisplatin (PC) for patients with advanced non-small cell lung cancer as the first-line regimen. Methods Ninety patients with previously untreated advanced non-small cell lung cancer were randomly assigned to receive either DC or PC. Patients received docetaxel 75mg/m2 on day 1 and cisplatin 75mg/m2 divided into two doses on days 2 to 3 in DC group and paclitaxel 150mg/m2 on day 1 and cisplatin 75mg/m2 divided into two doses on days 2 to 3 in PC group. The cycle of two regimens was repeated every 3 weeks. Response and toxicity were evaluated inpatients who completed two cycles of chemotherapy at least. Results Overall survival rate was 31.1% in DC group and 33.3 % in PC group. The median survival time was 10.2 months in DC group and 10.4 months in PC group.Median time to tumor progression was 4.4 months in DC group and 4.9 months in PC group. 1- and 2-year survival rate were 35.6% and 8.9% in DC group and 37.8% and 11.1% in PC group respectively. There were no significant differences in response rate, median survival time, median time to tumor progression and survival rate between two groups (P

The sympathetic nervous system regulates bone formation and resorption under physiological conditions. However, it is still unclear how the sympathetic nerves affect stem cell migration and differentiation in bone regeneration. Distraction osteogenesis is an ideal model of bone regeneration due to its special nature as a self-engineering tissue. In this study, a rat model of mandibular distraction osteogenesis with transection of cervical sympathetic trunk was used to demonstrate that sympathetic denervation can deplete norepinephrine (NE) in distraction-induced bone callus, down-regulate β3-adrenergic receptor (adrb3) in bone marrow mesenchymal stem cells (MSCs), and promote MSC migration from perivascular regions to bone-forming units. An in vitro Transwell assay was here used to demonstrate that NE can inhibit stroma-derived factor-1 (SDF-1)-induced MSC migration and expression of the migration-related gene matrix metalloproteinase-2 (MMP-2) and downregulate that of the anti-migration gene tissue inhibitor of metalloproteinase-3 (TIMP-3). Knockdown of adrb3 using siRNA abolishes inhibition of MSC migration. An in vitro osteogenic assay was used to show that NE can inhibit the formation of MSC bone nodules and expression of the osteogenic marker genes alkaline phosphatase (ALP), osteocalcin (OCN), and runt-related transcription factor-2 (RUNX2), but knockdown of adrb3 by siRNA can abolish such inhibition of the osteogenic differentiation of MSCs. It is here concluded that sympathetic denervation-induced MSC mobilization in rat mandibular distraction osteogenesis is associated with inhibition of MSC migration and osteogenic differentiation by NE/adrb3 in vitro. These findings may facilitate understanding of the relationship of MSC mobilization and sympathetic nervous system across a wide spectrum of tissue regeneration processes.