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Abstract The selection of viewpoints is a crucial aspect in conducting visual impact assessments of architectural heritage. To address this issue, a quantitative viewpoint selection method based on GIS spatial analysis is proposed. The first step involves defining the factors that influence the selection of viewpoints for architectural heritage. Next, the city’s historical architectural areas are divided into units based on courtyards. Subsequently, a candidate set of viewpoints is constructed by extracting the skeleton lines and characteristic points of sub-regions. Finally, following the principles of viewpoint selection, the method achieves the selection of viewpoints for the visual impact assessment of architectural heritage. The Forbidden City is chosen as the practical area for implementation, and the results demonstrate that the viewshed coverage range in the architectural heritage area is as high as 96%. It represents that this approach for visual impact assessments of architectural heritage is more grounded.

Abstract Background Children with cancer receiving chemotherapy commonly report a cluster of psychoneurological symptoms (PNS), including pain, fatigue, anxiety, depression, and cognitive dysfunction. The role of the gut microbiome and its functional metabolites in PNS is rarely studied among children with cancer. This study investigated the associations between the gut microbiome–metabolome pathways and PNS in children with cancer across chemotherapy as compared to healthy children. Methods A case–control study was conducted. Cancer cases were recruited from Children’s Healthcare of Atlanta and healthy controls were recruited via flyers. Participants reported PNS using the Pediatric Patient-Reported Outcomes Measurement Information System. Data for cases were collected pre-cycle two chemotherapy (T0) and post-chemotherapy (T1), whereas data for healthy controls were collected once. Gut microbiome and its metabolites were measured using fecal specimens. Gut microbiome profiling was performed using 16S rRNA V4 sequencing, and metabolome was performed using an untargeted liquid chromatography–mass spectrometry approach. A multi-omics network integration program analyzed microbiome–metabolome pathways of PNS. Results Cases (n = 21) and controls (n = 14) had mean ages of 13.2 and 13.1 years. For cases at T0, PNS were significantly associated with microbial genera (e.g., Ruminococcus, Megasphaera, and Prevotella), which were linked with carnitine shuttle (p = 0.0003), fatty acid metabolism (p = 0.001) and activation (p = 0.001), and tryptophan metabolism (p = 0.008). Megasphaera, clustered with aspartate and asparagine metabolism (p = 0.034), carnitine shuttle (p = 0.002), and tryptophan (p = 0.019), was associated with PNS for cases at T1. Gut bacteria with potential probiotic functions, along with fatty acid metabolism, tryptophan, and carnitine shuttle, were more clustered in cancer cases than the control network and this linkage with PNS needs further studies. Conclusions Using multi-omics approaches, this study indicated specific microbiome–metabolome pathways linked with PNS in children with cancer across chemotherapy. Due to limitations such as antibiotic use in cancer cases, these findings need to be further confirmed in a larger cohort.

Photoacoustic tomography (PAT) is an innovative biomedical imaging technology, which has the capacity to obtain high-resolution images of biological tissue. In the extremely limited-view cases, traditional reconstruction methods for photoacoustic tomography frequently result in severe artifacts and distortion. Therefore, multiple diffusion models-enhanced reconstruction strategy for PAT is proposed in this study. Boosted by the multi-scale priors of the sinograms obtained in the full view and the limited-view case of 240°, the alternating iteration method is adopted to generate data for missing views in the sinogram domain. The strategy refines the image information from global to local, which improves the stability of the reconstruction process and promotes high-quality PAT reconstruction. The blood vessel simulation dataset and the in vivo experimental dataset were utilized to assess the performance of the proposed method. When applied to the in vivo experimental dataset in the limited-view case of 60°, the proposed method demonstrates a significant enhancement in peak signal-to-noise ratio and structural similarity by 23.08 % and 7.14 %, respectively, concurrently reducing mean squared error by 108.91 % compared to the traditional method. The results indicate that the proposed approach achieves superior reconstruction quality in extremely limited-view cases, when compared to other methods. This innovative approach offers a promising pathway for extremely limited-view PAT reconstruction, with potential implications for expanding its utility in clinical diagnostics.

In this study, the effect of the degree of hard-phase fracture on the mechanical properties of accumulative-roll-bonded metal composite plates using experimental tests and finite element simulations. Ti–Al plates with two compositions, i.e., those with fractured and continuous intermediate Ti layers, were used as base materials and subjected to accumulative roll bonding five times. The results showed that the fracture of the intermediate Ti layer significantly degraded the mechanical properties. However, the more the Ti layer was broken down and distributed within the composite plate during accumulative roll bonding, the better were the mechanical properties. Tensile fracture of the composite plate only occurred in the Al phase, with the crack path deflected around the Ti phase. The more compact the Ti distribution, the more severe the tearing and delamination of the Al phase. Through finite element simulations, it was concluded that the shorter the distance between the Ti fragments along the loading direction, the higher the stress and the strain rate, which resulted in premature fracture and degradation of the mechanical properties.

Megaproject Social Responsibility (MSR) is widely acknowledged as contributing to project performance. However, the effect of Megaproject Social Responsibility Behavior (MSRB) implemented by organizations participating in construction on project performance remains a subject of considerable debate, and the intrinsic mechanism of MSRB’s effect on the performance of megaprojects has not been elucidated. Therefore, this study employs resource-based theory to investigate the mechanism underlying MSRB’s effect on project performance, taking into account both internal and external social capital as well as resource integration capacity as pivotal influences. Drawing on sample data from 206 experienced project managers across the various parties involved, this study develops a Bayesian network model to elucidate the MSRB effect mechanism. Through inference and sensitivity analysis, this study discovers variations in the enhancement effects across the four dimensions of MSRB on project performance. Notably, a combination strategy yields superior enhancement effects. Furthermore, when project performance is suboptimal, resource integration capacity emerges as a significant mediator between MSRB and project performance. Conversely, at high levels of project performance, MSRB directly contributes to enhancing project outcomes. The findings of this study offer valuable insights for the governance of MSR and the enhancement of project performance in megaprojects.

The genetically modified (GM) maize DBN9936 with a biosafety certificate will soon undergo commercial application. To monitor the safety of DBN9936 maize, three genomic DNA (gDNA) reference materials (RMs) (DBN9936a, DBN9936b, and DBN9936c) were prepared with nominal copy number ratios of 100%, 3%, and 1% for the DBN9936 event, respectively. DBN9936a was prepared from the leaf tissue gDNA of DBN9936 homozygotes, while DBN9936b and DBN9936c were prepared by the quantitative mixing of gDNA from the leaf tissues of DBN9936 homozygotes and non-GM counterparts. Validated DBN9936/zSSIIb duplex droplet digital PCR was demonstrated to be an accurate reference method for conducting homogeneity study, stability study, and collaborative characterization. The minimum intake for one measurement was determined to be 2 μL, and the gDNA RMs were stable during transport at 37 °C for 14 days and storage at −20 °C for 18 months. Each gDNA RM was certified for three property values: DBN9936 event copy number concentration, zSSIIb reference gene copy number concentration, and DBN9936/zSSIIb copy number ratio. The measurement uncertainty of the certified values took the uncertainty components related to possible inhomogeneity, instability, and characterization into account. This batch of gDNA RMs can be used for calibration and quality control when quantifying DBN9936 events.

Abstract Background Both schizophrenia (SZ) and overweight/obesity (OWB) have shown some structural alterations in similar brain regions. As higher body mass index (BMI) often contributes to worse psychiatric outcomes in SZ, this study was designed to examine the effects of OWB on gray matter volume (GMV) in patients with SZ. Methods Two hundred fifty subjects were included and stratified into four groups (n = 69, SZ patients with OWB, SZ-OWB; n = 74, SZ patients with normal weight, SZ-NW; n = 54, healthy controls with OWB, HC-OWB; and n = 53, HC with NW, HC-NW). All participants were scanned using high-resolution T1-weighted sequence. The whole-brain voxel-based morphometry was applied to examine the GMV alterations, and a 2 × 2 full factorial analysis of variance was performed to identify the main effects of diagnosis (SZ vs HC), BMI (NW vs OWB) factors, and their interactions. Further, the post hoc analysis was conducted to compare the pairwise differences in GMV alterations. Results The main effects of diagnosis were located in right hippocampus, bilateral insula, rectus, median cingulate/paracingulate gyri and thalamus (SZ

In this study, a skin gas detection system based on quartz enhanced photoacoustic spectroscopy (QEPAS) with a constant temperature collection chamber and an automatic frequency adjustment function was used to collect and monitor carbon dioxide (CO2) emissions from human skin. The detection element of the system is an on-beam structure assembled by a 30.72 kHz quartz tuning fork (QTF). A laser with a wavelength of 4991.26 cm−1 is emitted (with a wavelength adjustment range of 10 cm−1) to excite the QTF. When the integration time is 365 s, the system can achieve a minimum detection limit (MDL) of 2.6 ppmv. The sensitivity of the system is 636.9 ppmv/V. The gas detection system is used to monitor the concentration of CO2 emissions from different parts of the skin and the same part covered by different cosmetics. The CO2 emission rate is defined as the ratio of the skin gas monitoring time of 25 min to the CO2 concentration variable in the gas chamber (volume of 8 mL). The results were collected from three healthy volunteers. Among the six different parts, the cheeks emitted the fastest rate (the average rate was 365.5 ppmv/min) of CO2, and the thighs emitted the slowest rate (the average rate was 56.4 ppmv/min) of CO2. Comparing the experimental results of the six sites at different times, the order of the CO2 emission rate is identical for all six sites. In the experiments with the three cosmetic products (experimental site: forearm), comparing the CO2 emission rate from clean skin with the CO2 emission rate from cosmetic-covered skin shows that sunscreen is the most breathable, followed by barrier cream, and foundation is the least breathable.

BackgroundRemarkably, the anti-cancer efficacy of immunotherapy in lung adenocarcinoma (LUAD) has been demonstrated. However, predicting the beneficiaries of this expensive treatment is still a challenge.Materials and methodsA group of patients (N = 250) diagnosed with LUAD and receiving immunotherapy were retrospectively studied. They were randomly divided into a training dataset (80%) and a test dataset (20%). The training dataset was utilized to train neural network models to predict patients’ objective response rate (ORR), disease control rate (DCR), responders (progression-free survival time > 6 months), and overall survival (OS) possibility, which were validated by both the training and test datasets and packaged into a tool later.ResultsIn the training dataset, the tool scored 0.9016 area under the receiver operating characteristic (AUC) curve on ORR judgment, 0.8570 on DCR, and 0.8395 on responder prediction. In the test dataset, the tool scored 0.8173 AUC on ORR, 0.8244 on DCR, and 0.8214 on responder determination. As for OS prediction, the tool scored 0.6627 AUC in the training dataset and 0.6357 in the test dataset.ConclusionsThis immunotherapy efficacy predictive tool for LUAD patients based on neural networks could predict their ORR, DCR, and responder well.

IntroductionInflammation play important roles in the initiation and progression of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), septic shock, clotting dysfunction, or even death associated with SARS-CoV-2 infection. However, the pathogenic mechanisms underlying SARS-CoV-2-induced hyperinflammation are still largely unknown.MethodsThe animal model of septic shock and ALI was established after LPS intraperitoneal injection or intratracheal instillation. Bone marrow-derived macrophages (BMDMs) from WT and BPOZ-2 KO mouse strains were harvested from the femurs and tibias of mice. Immunohistology staining, ELISA assay, coimmunoprecipitation, and immunoblot analysis were used to detect the histopathological changes of lung tissues and the expression of inflammatory factors and protein interaction.Results and conclusionsWe show a distinct mechanism by which the SARS-CoV-2 N (SARS-2-N) protein targets Bood POZ-containing gene type 2 (BPOZ-2), a scaffold protein for the E3 ubiquitin ligase Cullin 3 that we identified as a negative regulator of inflammatory responses, to promote NLRP3 inflammasome activation. We first demonstrated that BPOZ-2 knockout (BPOZ-2 KO) mice were more susceptible to lipopolysaccharide (LPS)-induced septic shock and ALI and showed increased serum IL-1β levels. In addition, BMDMs isolated from BPOZ-2 KO mice showed increased IL-1β production in response to NLRP3 stimuli. Mechanistically, BPOZ-2 interacted with NLRP3 and mediated its degradation by recruiting Cullin 3. In particular, the expression of BPOZ-2 was significantly reduced in lung tissues from mice infected with SARS-CoV-2 and in cells overexpressing SARS-2-N. Importantly, proinflammatory responses triggered by the SARS-2-N were significantly blocked by BPOZ-2 reintroduction. Thus, we concluded that BPOZ-2 is a negative regulator of the NLPR3 inflammasome that likely contributes to SARS-CoV-2-induced hyperinflammation.

Due to their exceptional all-around performance, steel/aluminum-alloy composite plates have been frequently utilized in many different industries. However, when steel/aluminum-alloy composite plates are prepared by the rolling process, they will scarcely bond with high bonding strength under a lower reduction rate due to the inconsistent deformation the of steel/aluminum-alloy. Therefore, a method of adding a pure-aluminum interlayer by differential temperature rolling with induction heating was proposed to prepare steel/aluminum-alloy composite plates. The results showed that when the induction heating time was 10–18 s, the pure-aluminum interlayer became molten, and the temperature difference between the steel and aluminum alloy reached 350–500 °C. The interface shear strength of the composite plate reached more than 68 MPa under a 31% reduction rate. The shear fracture of the composite plate occurred in the pure-aluminum layer, and the steel/aluminum interface diffusion layer was 0.83–0.99 μm thick. There was no obvious compound formation at the bonding interface, however, the steel and aluminum alloy could not bond without the addition of an interlayer under the same conditions.

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 Polydopamine (PDA), which is derived from marine mussels, has excellent potential in early diagnosis of diseases and targeted drug delivery owing to its good biocompatibility, biodegradability, and photothermal conversion. However, when used as a solid nanoparticle, the application of traditional PDA is restricted because of the low drug-loading and encapsulation efficiencies of hydrophobic drugs. Nevertheless, the emergence of mesoporous materials broaden our horizon. Mesoporous polydopamine (MPDA) has the characteristics of a porous structure, simple preparation process, low cost, high specific surface area, high light-to-heat conversion efficiency, and excellent biocompatibility, and therefore has gained considerable interest. This review provides an overview of the preparation methods and the latest applications of MPDA-based nanodrug delivery systems (chemotherapy combined with radiotherapy, photothermal therapy combined with chemotherapy, photothermal therapy combined with immunotherapy, photothermal therapy combined with photodynamic/chemodynamic therapy, and cancer theranostics). This review is expected to shed light on the multi-strategy antitumor therapy applications of MPDA-based nanodrug delivery systems. Graphical Abstract

BackgroundAt present, immunotherapy is a very promising treatment method for lung cancer patients, while the factors affecting response are still controversial. It is crucial to predict the efficacy of lung squamous carcinoma patients who received immunotherapy.MethodsIn our retrospective study, we enrolled lung squamous carcinoma patients who received immunotherapy at Beijing Chest Hospital from January 2017 to November 2021. All patients were grouped into two cohorts randomly, the training cohort (80% of the total) and the test cohort (20% of the total). The training cohort was used to build neural network models to assess the efficacy and outcome of immunotherapy in lung squamous carcinoma based on clinical information. The main outcome was the disease control rate (DCR), and then the secondary outcomes were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).ResultsA total of 289 patients were included in this study. The DCR model had area under the receiver operating characteristic curve (AUC) value of 0.9526 (95%CI, 0.9088–0.9879) in internal validation and 0.9491 (95%CI, 0.8704–1.0000) in external validation. The ORR model had AUC of 0.8030 (95%CI, 0.7437–0.8545) in internal validation and 0.7040 (95%CI, 0.5457–0.8379) in external validation. The PFS model had AUC of 0.8531 (95%CI, 0.8024–0.8975) in internal validation and 0.7602 (95%CI, 0.6236–0.8733) in external validation. The OS model had AUC of 0.8006 (95%CI, 0.7995–0.8017) in internal validation and 0.7382 (95%CI, 0.7366–0.7398) in external validation.ConclusionsThe neural network models show benefits in the efficacy evaluation of immunotherapy to lung squamous carcinoma patients, especially the DCR and ORR models. In our retrospective study, we found that neoadjuvant and adjuvant immunotherapy may bring greater efficacy benefits to patients.

Background and objective Immune checkpoint inhibitor monotherapy is reported to have little effect in advanced non-small cell lung cancer (NSCLC) patients with driver oncogenes. However, recent studies have shown that some patients with driver genes are still benefit from combination immunotherapy after tyrosine kinase inhibitors (TKIs) drug resistance. The purpose of this study was to analyze the efficacy of posterior line immunotherapy in NSCLC patients with epidermal growth factor (EGFR) sensitive mutation, and to evaluate the value of immunotherapy in posterior line therapy in patients with advanced EGFR mutation. Methods A total of 27 patients with EGFR mutation diagnosed in Beijing Chest Hospital, Capital Medical University from June 2018 to November 2020 were collected. After the progress of targeted therapy, they had received programmed cell death protein 1 (PD-1) checkpoint inhibitor combined with chemotherapy and anti-angiogenic drug therapy. Results Of the 27 advanced NSCLC patients, 19 cases (70.4%) did not have T790M mutation. There were 8 cases (29.6%) with T790M point mutation. The total objective response rate (ORR) was 40.7%. Kaplan-Meier survival analysis showed that there was no statistically significant difference among different EGFR mutations (χ2=4.15, P=0.230). But progression-free survival (PFS) was significantly longer in patients without T790M mutation than in patients with T790M mutation (9.2 mon vs 3.3 mon, χ2=2.808, P=0.041), and the same trend was observed in patients with overall survival treated with the PD-1 inhibitor (12.2 mon vs 7.3 mon, χ2=3.22, P=0.062). ORR of patients without T790M was significantly better than that with T790M (52.63% vs 12.5%, P=0.045). Conclusion Patients with EGFR mutation can benefit from later-line combined immunotherapy. The patients with T790M mutation in the population of EGFR mutation had the worst effect of immunotherapy in the later line. Therefore, the follow-up treatment and whole-course management of these patients need to explore better treatment strategies to improve the benefit.

Background and objective Immunotherapy represented by immune checkpoint inhibitors (ICIs) has been widely used in the treatment of lung cancer. There are controversies in clinical practice for patients with advanced non-small cell lung cancer (NSCLC) and high programmed cell death-ligand 1 (PD-L1) expression receiving ICIs monotherapy or combination chemotherapy. Methods This study retrospectively analyzed the clinical data of 49 patients with advanced NSCLC and high PD-L1 expression. Immunohistochemistry was performed with 22C3 antibody, and the expression level of PD-L1 was evaluated according to tumor proportion score (TPS). Objective response rate (ORR) and progression free survival (PFS) were compared by groups of different clinical characteristics. Results ORR of monotherapy and combination therapy group was 47.1% (8/17) and 43.8% (14/32), respectively, without statistical difference (P=0.825). The median PFS of monotherapy and combination therapy group was 8.0 months and 6.8 months, respectively, without statistical difference (P=0.502). Statistical analysis of predictors of immunotherapy for the patients showed first-line immunotherapy had better ORR than subsequent immunotherapy (12/19, 63.2% vs 10/30, 33.3%, P=0.041), however no difference in PFS. And there were no differences in ORR or PFS among groups of age, gender, smoking status, performance status (PS), pathological type, tumor size and tumor-node-metastasis (TNM) stage. Conclusion The therapeutic effect is similar between ICIs monotherapy and combination chemotherapy for patients with advanced NSCLC and high PD-L1 expression. ORR of first-line immunotherapy was better in patients with advanced NSCLC and high PD-L1 expression. The optimal treatment for this population remains further prospective clinical studies.

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.

To develop a simple and fast method for screening genetically modified ingredients from processing by-product and waste, direct quantitative PCR (qPCR) kit-Taqman which omitting multi genomic DNA preparing steps was developed in this study. A total of 18 oil crop processing by-products and wastes including 10 soybean and 8 cotton materials were collected from food processing factories. Compared with 2 commercial direct qPCR kits, conditions of DNA releasing procedure and PCR amplification were optimized. Element screening was performed at the initial step of genetically modified (GM) ingredient testing procedure via direct qPCR. GM event identification was carried out in positive samples by initial screening. Totally 5 screening elements (P–35S, T-NOS, Cp4-epsps, bar and pat) for soybean materials and 6 screening elements (P–35S, T-NOS, NPTII, Cry1Ac, bar and pat) for cotton samples were detected. In GM event identification, MON531 and MON1445 were found in cotton materials. Results were further confirmed by real-time PCR with DNA extraction and purification. The direct qPCR system proposed by this research was convenient for rapid screening and identification of GM ingredients in oil crop primary by-product and waste.

In polymerase chain reaction (PCR)-based nucleic acid quantification, the DNA template type, primer/probe sequence, and instrument platform such as real-time quantitative PCR (qPCR) and digital PCR (dPCR) affect the accuracy and reliability of quantitative results. In this study, a plasmid DNA (pDNA) pBI121-screening, genetically modified (GM) rice SDrice genomic DNA (gDNA), and GM rapeseed SDrape gDNA, all carrying the same 11 screening elements, were used to prepare samples of different levels of gDNA and pDNA in a non-GM gDNA background. The comparison of the dPCR assays targeting the 11 screening elements revealed that the primer/probe set is a key factor that affects the accuracy of dPCR quantification. The optimal PCR method for the 11 screening elements was screened out from among the validated qPCR methods. The accuracy of the qPCR quantification of the low-level pDNA and gDNA test samples was low when pDNA was used as a calibrator, whereas that of the dPCR quantification was high and not affected by variations in template type and detection target. The validated dPCR assays targeting one or two elements can be randomly selected to characterize multiple-target pDNA reference materials (RMs). Low-level pDNA RMs with certified values can be used as quality controls for dPCR assays to avoid significant bias in gDNA quantification.

Objective: To investigate the clinical effects of the use of portable pulmonary function tester in patients with stable Chronic Obstructive Pulmonary Disease (COPD). Methods: A total of 80 patients with stable COPD were enrolled in our hospital from March 2018 to March 2019. They were divided into two groups according to different treatment methods. The comparison group was used for routine pulmonary function training, and the intervention group was trained for Portable Pulmonary Function Training and Test Device (PPFTTD). Comparison was made of forced expiratory volume in one second/forced vital capacity (FEV1/FVC), measured/predicted value of the first second forced expiratory volume (FEV1 measured/predicted value), measured/predicted value of maximal voluntary ventilation per minute between the two groups. Quality of life (QOL) scores such as daily living ability, social activity, depressive psychological symptoms, and anxiety psychological symptoms were measured. Results: The FEV1/FVC value, measured/predicted value of FEV1 and MVV of intervention group were higher than those in the comparison group (P

Background: Information regarding the localization of gastrointestinal perforation is crucial for the following surgical procedure. This study was to determine the key indicators and develop a prediction model for the localization in neonates with gastrointestinal perforation.Methods: A nomogram to predict the location of neonatal gastrointestinal perforation was developed using a cohort of patients who underwent surgery between July 2009 and May 2021. Baseline variables were analyzed using logistics regression and nomogram developed using significant predictors. The predictive performance of the nomogram was assessed by the concordance index (C-index), calibration curve, and area under the receiver operating characteristic (ROC) curve (AUC). The nomogram was further validated in an integrated external cohort.Results: We investigated the data of 201 patients, of which 65 (32.3%) were confirmed with upper gastrointestinal perforation by surgery. Multivariate logistic regression analysis identified the following as independent predictors: preterm [OR: 5.014 (1.492–18.922)], time of onset [OR: 0.705 (0.582–0.829)], preoperative hemoglobin [OR:1.017 (1.001–1.033)], bloody stool: No [OR: 4.860 (1.270–23.588)], shock [OR: 5.790 (1.683–22.455)] and sepsis: No [OR 3.044 (1.124–8.581)]. Furthermore, the nomogram was effective in predicting the perforation site, with an AUC of 0.876 [95% confidence interval (CI): 0.830–0.923]. Internal validation showed that the average AUC was 0.861. Additionally, the model achieved satisfactory discrimination (AUC, 0.900; 95% CI, 0.826–0.974) and calibration (Hosmer-Lemeshow test, P = 0.4802) in external validation.Conclusions: The nomogram based on the six factors revealed good discrimination and calibration, suggesting good clinical utility. The nomogram could help surgeons predict the location of gastrointestinal perforation before surgery to make a surgical plan.

The hygromycin phosphotransferase (HPT) gene as a selective marker is normally used in screening tests as a first step in detecting and quantifying genetically modified organisms (GMOs) in seeds, food, and feed materials. Nevertheless, if researchers only focus on the HPT gene, it is difficult to distinguish genetically modified (GM) crops from microbial infection, leading to miscalculation of the rate of GM materials in a given sample set. Here, we cloned the 7259 bp sequence carrying the HPT gene from soybean sprouts using the genome walking strategy. BLAST analysis revealed that this sequence was derived from plasmids naturally occurring in microorganisms, such as Escherichia coli, Klebsiella pneumoniae or Salmonella sp. Using the reconstructed plasmid pFP-hpt, qualitative PCR and quantitative real-time PCR (qPCR) methods were established, and 261 bp and 156 bp products were produced. The specificity of these assays was assessed against related pFP-hpt plasmids, plant species with important agronomic traits, and GM crops containing the HPT gene. No unexpected results were observed between samples using these qualitative PCR and qPCR methods. The sensitivity of this qualitative PCR assay was determined at 20 copies, while the limit of detection (LOD) and limit of quantification (LOQ) of qPCR were both 5 copies per reaction. Our in-house validation indicated that the amplification efficiency, linearity, and repeatability of this qPCR assay were in line with performance requirements. Furthermore, a qualitative and quantitative duplex PCR showed high reliability for the simultaneous detection of the HPT gene in a plant sample and environmental micro-organisms harboring the HPT gene in one PCR reaction. These qualitative PCR and qPCR assays were able to differentiate between plants infected with E. coli harboring the HPT gene from GM plants, indicating that these two methods are broadly applicable for routine GMO testing.

Abnormal pulmonary arterial vascular smooth muscle cells (PASMCs) proliferation is critical pathological feature of pulmonary vascular remodeling that acts as driving force in the initiation and development of pulmonary arterial hypertension (PAH), ultimately leading to pulmonary hypertension. Aloperine is a main active alkaloid extracted from the traditional Chinese herbal Sophora alopecuroides and possesses outstanding antioxidation and anti-inflammatory effects. Our group found Aloperine has protective effects on monocroline-induced pulmonary hypertension in rats by inhibiting oxidative stress in previous researches. However, the anti-inflammation effects of Aloperine on PAH remain unclear. Therefore, to further explore whether the beneficial role of Aloperine on PAH was connected with its anti-inflammatory effects, we performed experiments in vitro. Aloperine significantly inhibited the proliferation and DNA synthesis of human pulmonary artery smooth muscle cells (HPASMCs) induced by platelet-derived growth factor-BB, blocked progression through G0/G1to S phase of the cell cycle and promoted total ratio of apoptosis. In summary, these results suggested that Aloperine negatively regulated nuclear factor-κB signaling pathway activity to exert protective effects on PAH and suppressed HPASMCs proliferation therefore has a potential value in the treatment of pulmonary hypertension by negatively modulating pulmonary vascular remodeling.

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.

As the cultivation scale of genetically modified (GM) crops strongly increases, a convenient DNA assay is highly demanded in resource-limited areas. A label-free electrochemical impedance (EI) genosensor using gold carbon dots (GCDs) was developed with easy-to-use portable device. GCDs were used to modify screen-printed carbon electrode and immobilize capture probes by conducting a simple protocol. After the amplification products anchored on the sensor surface via hybridization reactions, the EI signal increased due to the formation of biocomplex hampering the interfacial electron transfer. Under the optimal conditions, the proposed genosensor coupled with recombinase polymerase amplification (RPA) could detect maize Ruifeng12-5 in a linear range of 0.10–5.0% with a detection limit of 0.10%. In addition, combined with a one-step extraction and RPA amplification, the proposed sensor device can be applied in resource-limited laboratories without expensive instruments or professionals. Therefore, the developed method provides an easy-to-use and sensitive platform for GM organism detection.

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.

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

Genome-edited plants created by genome editing technology have been approved for commercialization. Due to molecular characteristics that differ from classic genetically modified organisms (GMOs), establishing regulation-compliant analytical methods for identification and quantification of genome-edited plants has always been regarded as a challenging task. An editing-site-specific PCR method was developed based on the unique edited sequence in CAO1-edited rice plants. Test results of seven primer/probe sets indicated that this method can identify specific CAO1-edited rice from other CAO1-edited rice and wild types of rice with high specificity and sensitivity. The use of LNA (locked nucleic acid) in a probe can efficiently increase the specificity of the editing-site-specific PCR method at increased annealing temperature which can eliminate non-specific amplification of the non-target. The genome-edited ingredient content in blinded samples at the level of 0.1% to 5.0% was accurately quantified by this method on the ddPCR platform with RSD of

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

The purpose of this study was to evaluate the efficacy and safety of Uyghur medical formula Loki zupa in patients with chronic asthma. Adult patients with chronic asthma randomly received placebo or Loki zupa as add-on to inhaled corticosteroids (ICS) maintenance treatment. Loki zupa or mimics was administered orally 10 ml per time, three times a day for 8 weeks. The primary endpoints were asthma control test (ACT) score and peak expiratory flow (PEF). The secondary endpoints were acute exacerbation rate, lung function, night waking days, and symptom-free days in the near 2 weeks, Asthma Quality of Life Questionnaire (AQLQ) score and some inflammatory cytokines in peripheral blood. A total of 240 adult patients with chronic asthma were enrolled, and 218 patients were randomized to placebo (n = 109) or Loki zupa (n = 109) in addition to ICS for 8 weeks. Treatment with Loki zupa resulted in significant improvement in ACT score compared to the placebo group (p = 0.002). Furthermore, oral taken of Loki zupa increased the PEF obviously (p = 0.026). Loki zupa treatment did not improve the forced expiratory volume in 1 s (FEV1, p = 0.131) and FEV1/FVC compared to the placebo treatment (p = 0.805). The placebo group had higher rates of acute exacerbations than the Loki zupa group (6.3% vs. 0, p = 0.027). Subjects randomized to Loki zupa had increased daytime symptom-free days within 2 weeks than placebo (p = 0.016). However, Loki zupa had no effect on night waking days in the near 2 weeks (p = 0.369) and AQLQ score (p = 0.113). No significant effect was found on inflammatory cytokines (IL-2, IL-4, IL-5, IL-10, IL-13, IL-17, IL-33, IFN-γ, and TGF-β) between the two groups (p > 0.05). No adverse events and severe asthma exacerbations were recorded in the two groups (p > 0.05). Loki zupa add-on to standard ICS produced clinically significant improvements in ACT score, PEF, daytime symptom-free days and acute exacerbation in patients with chronic asthma.Clinical trial: This study is registered at http://www.chictr.org.cn/ with identifier number ChiCTR-IPR-16008106.

Chromosome dynamics during meiotic prophase I are associated with a series of major events such as chromosomal reorganization and condensation, pairing/synapsis and recombination of the homologs, and chromosome movements at the nuclear envelope (NE). The NE is the barrier separating the nucleus from the cytoplasm and thus plays a central role in NE-associated chromosomal movements during meiosis. Previous studies have shown in various species that NE-linked chromosome dynamics are actually driven by the cytoskeleton. The linker of nucleoskeleton and cytoskeleton (LINC) complexes are important constituents of the NE that facilitate in the transfer of cytoskeletal forces across the NE to individual chromosomes. The LINCs consist of the inner and outer NE proteins Sad1/UNC-84 (SUN), and Klarsicht/Anc-1/Syne (KASH) domain proteins. Meiosis-specific adaptations of the LINC components and unique modifications of the NE are required during chromosomal movements. Nonetheless, the actual role of the NE in chromosomic dynamic movements in plants remains elusive. This review summarizes the findings of recent studies on meiosis-specific constituents and modifications of the NE and corresponding nucleoplasmic/cytoplasmic adaptors being involved in NE-associated movement of meiotic chromosomes, as well as describes the potential molecular network of transferring cytoplasm-derived forces into meiotic chromosomes in model organisms. It helps to gain a better understanding of the NE-associated meiotic chromosomal movements in plants.

In order to obtain higher data transmission speed and greater array gain，a precoding algorithm based on max-SNR in massive MIMO system was proposed.The basic method of this algorithm was following.Firstly，the base station obtained MMSE channel estimation by received uplink pilot sequences，then the base station transmited downlink data to users after precoding.Terminal users derived the optimal precoding matrix by resolving a Rayleigh entropy optimization problem based on the received SNR.Simulation results show that the performance of the proposed algorithm is better than SVD algorithm，especially when the number of transmit antennas is large，the proposed algorithm is valuable in massive MIMO systems in the future.

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.

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.

This work reveals first principle results of the endohedral fullerenes made from neutral or charged single atomic lithium (Li or Li+) encapsulated in fullerenes with various cage sizes. According to the calculated binding energies, it is found that the encapsulation of a single lithium atom is energetically more favorable than that of lithium cation. Lithium, in both atomic and cationic forms, exhibits a clear tendency to depart from the center in large cages. Interaction effects dominate the whole encapsulation process of lithium to carbon cages. Further, the nature of the interaction between Li (or Li+) and carbon cages is discussed based on reduced density gradient, energy decomposition analysis, and charge transfer.

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

We report an advanced stage Chinese female lung adenocarcinoma patient who was negative for epidermal growth factor receptor (EGFR), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations, also negative for chinodem microtubule-associated protein-like 4/anaplastic lymphoma kinase (EML4-ALK) gene rearrangement and treated with bevacizumab (15 mg/kg) in combination with 6 cycles of conventional doses of paclitaxel and carboplatin chemotherapy. She was then treated with maintenance bevacizumab for a total of 42 cycles, the total dose of bevacizumab is 44,730 mg. The progression-free survival was 39 months. Our findings suggest that maintenance bevacizumab for the treatment of non-small cell lung cancer (NSCLC) is safe and its benefit for long-term survival overwhelms its side effects.

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 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.

Because of the age of relics and the lack of historical data, the geometric forms of missing parts can only be judged by the subjective experience of repair personnel, which leads to varying restoration effects when the geometric structure of the complex relic is reconstructed. Therefore, virtual repair effects cannot fully reflect the historical appearance of cultural relics. In order to solve this problem, this paper presents a virtual restoration method based on the multiscale spatial geometric features of cultural relics in the case of complex construction where the geometric shape of the damaged area is unknown, using the Dazu Thousand-Hand Bodhisattva statue in China as an example. In this study, the global geometric features of the three-dimensional (3D) model are analyzed in space to determine the geometric shape of the damaged parts of cultural relics. The local geometric features are represented by skeleton lines based on regression analysis, and a geometric size prediction model of the defective parts is established, which is used to calculate the geometric dimensions of the missing parts. Finally, 3D surface reconstruction technology is used to quantitate virtual restoration of the defective parts. This method not only provides a new idea for the virtual restoration of artifacts with complex geometric structure, but also may play a vital role in the protection of cultural relics.

Background and objective Erlotinib is a small molecular inhibitor of tyrosine kinase. One study has confirmed that it can prolong the median progression-free survival time (PFS), and can improve the one-year survival rate of patients with advanced non-small cell lung cancer. The aim of this trial is to evaluate the response and adverse reaction of agent erlotinib in advanced and previously treated non-small-cell lung cancer. Methods The study was one part of the EAP (Expanded Access Programme) study. Forty-five patients with advanced non-small cell lung cancer, which had been treated with 1-2 regimens containing platinum previously, were treated with erlotinib from Dec 2005. Erlotinib was prescribed at a dose of 150 mg daily. Results Forty-three patients were evaluated response and all patients were evaluated toxicity. Among these patients, CR 0 case, PR 19 cases (44.2%), RR (CR+PR) 44.2% and SD 13 cases as their best response, disease control rate (DCR=CR+PR+SD) 74.4%, PD 11cases (25.6%). The median progression-free survival time was 4.8 months; the median survival time was 15.0 months; the one-year survival rate was 68.8% (31/45). The median PFS of patients with adenocarcinoma and with non-adenocarcinoma was 7.6 months vs 2.6 months (P=0.018). The drug-related adverse reactions were skin rash (41 cases, 91.1%), billirubine increased (15 cases, 33.3%), ALT increased (9 cases, 20%) and diarrhea (4 cases, 8.9%). For patients with and without skin rash, the median PFS was 7.5 months vs 1.1 months (P=0.001), and the median survival time was 15.6 months vs 5.2 months (P=0.002). Conclusion Erlotinib is effective in advanced and previously treated non-small cell lung cancer, and it is much more effective in adenocarcinoma and patients with skin rash. It is well tolerated, only with some minimal adverse reactions.

Background and objectives It has been proven that epigermal growth factor receptor (EGFR) signal pathway plaied an important role in the oncogenesis and development of non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (EGFR-TKIs) are currently investigated in the treatment of NSCLC. It was suggested in previous studies that the EGFR gene mutations were correlated with the response to EGFR-TKIs therapy and prognosis of NSCLC. We studied the role of EGFR gene mutations in response to two kinds of TKIs therapy and prognosis of NSCLC in this study. Methods The tissue samples of 59 advanced NSCLC patients (34 patients receiving Gefitinib monotherapy and 25 patients receiving Erlotinib monotherapy) were collected, and patient charts were reviewed. The mutations in exons 19 and 21 of EGFR gene were detected by PCR-PAGE and PCR-RFLP respectively. The sequences of interested fragments were verified by direct sequencing. Relationship between EGFR mutation and response to TKIs therapy was analyzed with X^2 test. Results EGFR gene mutations were identified in 22 of 59 samples (37.3%). EGFR gene mutation rate was significantly higher in female, non-smoker and patients with adenocarcinoma than in others (50% vs 18.9%, P0.05). Conclusions EGFR gene mutation occurs more frequently in female, non-smoker and patients with adenocarcinoma. In patients with advanced NSCLC, EGFR mutation is associated with good response to EGFR-TKIs therapy.

Plant non-specific lipid transfer proteins (nsLTPs) constitute large multigene families that possess complex physiological functions, many of which remain unclear. This study isolated and characterized the function of a lipid transfer protein gene, BraLTP1 from Brassica rapa, in the important oilseed crops Brassica napus. BraLTP1 encodes a predicted secretory protein, in the little known VI Class of nsLTP families. Overexpression of BnaLTP1 in B. napus caused abnormal green coloration and reduced wax deposition on leaves and detailed wax analysis revealed 17-80% reduction in various major wax components, which resulted in significant water-loss relative to wild type. BnaLTP1 overexpressing leaves exhibited morphological disfiguration and abaxially curled leaf edges, and leaf cross-sections revealed cell overproliferation that was correlated to increased cytokinin levels (tZ, tZR, iP, and iPR) in leaves and high expression of the cytokinin biosynthsis gene IPT3. BnaLTP1-overexpressing plants also displayed morphological disfiguration of flowers, with early-onset and elongated carpel development and outwardly curled stamen. This was consistent with altered expression of a a number of ABC model genes related to flower development. Together, these results suggest that BraLTP1 is a new nsLTP gene involved in wax production or deposition, with additional direct or indirect effects on cell division and flower development.

Background and objective Erlotinib is a small molecular inhibitor of tyrosine kinase. Multiple foreign and demestic studies have confirmed that it can prolong the median progression-free survival time (PFS) and the overall survival (OS), which could be more significant in the selected population. In this study we retrospectively oberserved the response, the survival and adverse reaction of erlotinib in non-selected non-small cell lung cancer. Methods The retrospective study included seventy non-small-cell lung cancer patients, who were treated with erlotinib from July 2005 to July 2009. Erlotinib was prescribed at a dose of 150 mg daily. Results Sixty-eight patients were evaluated response. Among these patients, CR 0 case, PR 26 cases, RR (CR+PR) 38.2% and SD 24 cases as their best response, disease control rate (DCR=CR+PR+SD) 73.5%, PD 18 cases (26.5%). Sixty-three patients were evaluated PFS. The median PFS was 3.0 months. The median PFS of adenocarcinoma and non-adenocarcinoma was 3.0 months vs 2.6 months. The drug-related adverse reactions were skin rash , diarrhea and interstitial lung disease (ILD)(4.3%). Conclusion Erlotinib is active in non-small cell lung cancer, and it is much more effective in adenocarcinoma and non-smoking patients. There is no difference in response or suvival concerning the sexuality. It is well tolerated in most patients.

The timely detection of gold foil damage in gold-overlaid stone carvings and the associated maintenance of these relics pose several challenges to both the research and heritage protection communities internationally. This paper presents a new method for detecting gold foil damage by making use of multi-temporal 3D LiDAR point clouds. By analyzing the errors involved in the detection process, a formula is developed for calculation of the damage detection threshold. An improved division method for the linear octree that only allocates memory to the non-blank nodes, is proposed, which improves storage and retrieval efficiency for the point clouds. Meanwhile, the damage-occurrence regions are determined according to Hausdorff distances. Using a triangular mesh, damaged regions can be identified and measured in order to determine the relic’s total damaged area. Results demonstrate that this method can effectively detect gold foil damage in stone carvings. The identified surface area of damaged regions can provide the information needed for subsequent restoration and protection of relics of this type.