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Image deblurring is a fundamental and challenging low-level vision problem. Previous vision research indicates that edge structure in natural scenes is one of the most important factors to estimate the abilities of human visual perception. In this paper, we resort to human visual demands of sharp edges and propose a two-phase edge-aware deep network to improve deep image deblurring. An edge detection convolutional subnet is designed in the first phase and a residual fully convolutional deblur subnet is then used for generating deblur results. The introduction of the edge-aware network enables our model with the specific capacity of enhancing images with sharp edges. We successfully apply our framework on standard benchmarks and promising results are achieved by our proposed deblur model.

Background: Lung adenocarcinoma (LUAD) has a complex tumor heterogeneity. This study aimed to identify LUAD subtypes and build a reliable prognostic signature based on the activity changes of the hallmark and immunologic gene sets. Methods: Changes in the activities of the hallmark and immunologic gene sets were analyzed based on The Cancer Genome Atlas (TCGA)-LUAD dataset, followed by identification of prognosis-related differential gene sets (DGSs) and their related LUAD subtypes. Survival analysis, correlation with clinical characteristics, and immune microenvironment assessment for subtypes were performed. Moreover, the DGSs among different subtypes were identified, followed by the construction and evaluation of a prognostic risk score model and nomogram. The tumor mutation burden (TMB) of different risk groups wascompared. Results: Two LUAD subtypes were identified based on the activity changes of the hallmark and immunologic gene sets. Cluster 2 had worse prognosis, more advanced tumorand clinical stages, and higher immune infiltration than cluster 1. Moreover, a prognostic risk score signaturewas established using two LUAD subtype-related DGSs, which could stratify patients at different risk levels. A shorter survival time and higher TMB levels were observed in the high-risk patients. The established nomogram accurately predicted the survival outcomes. Conclusions: Our findings revealed that our constructed prognostic signature could accurately predict the survival outcomes and immune microenvironment of patients with LUAD, which was helpful in predicting the prognosis and guiding personalized therapeutic strategies for LUAD.

Platinum-based chemotherapy is the standard first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). In this phase 3 study (ClinicalTrial.gov: NCT03829969), 514 patients with treatment-naïve advanced ESCC were randomized (1:1) to receive toripalimab or placebo in combination with paclitaxel plus cisplatin (TP) every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS is observed for the toripalimab arm over the placebo arm (hazard ratio [HR] = 0.58; 95% CI, 0.46-0.74; p 0.0001). The prespecified interim analysis of overall survival (OS) also reveals a significant OS improvement for patients treated with toripalimab plus TP over placebo plus TP (HR = 0.58; 95% CI, 0.43-0.78; p = 0.0004). The incidences of grade ≥3 treatment-emergent adverse events are similar between the two arms. Toripalimab plus TP significantly improves PFS and OS in patients with treatment-naïve, advanced ESCC, with a manageable safety profile.

Being one of the most lethal cancers that exhibit high levels of heterogeneity, hepatocellular carcinoma (HCC) is associated with diverse oncogenic pathways underpinned by varied driver genes. HCC can be induced by different etiological factors including virus infection, toxin exposure or metabolic disorders. Consequently, patients may display varied genetic profiles, and may respond differently to the treatments involving inhibition of target pathways. These DNA/RNA mutations, copy number variations, chromatin structural changes, aberrant expression of non-coding RNAs and epigenetic modifications were considered as biomarkers in the application of precision medication. To explore how genetic testing could contribute to early diagnosis, prognosis, treatment and postoperative monitoring of HCC, we conducted a systematic review of genetic markers associated with different pathologies. Moreover, we summarized on-going clinical trials for HCC treatment, including the trials for multiple kinase inhibitors and immune checkpoint blockade (ICB). The efficacy of ICB treatment in HCC is not as good as what was observed in lung cancer and melanoma, which might be due to the heterogeneity of the microenvironment of the liver.

Background: The epidermal growth factor receptor (EGFR) is one of the most commonly altered genes in non-small cell lung cancer(NSCLC). Of these, insertion mutation in 20 exon (Ex20ins) of the EGFR occurs less frequently. In comparison with the common EGFR mutations (19Del/L858R), the NSCLC patients with Ex20ins have a worse prognosis. Recently, the FDA approved targeted oral therapeutic agent for NSCLC patients with EX20ins mutation, which has markedly improved their survival. Here we carry out a complete analysis of the frequency and types of EGFR 20 Exon insertion mutations in the large-scale NSCLC cohort of the Chinese population. Methods: From January 2020 to October 2021, a total of 4,091 patients were confirmed as NSCLC were included in the study. The Next-generation sequencing was utilized for detecting genetic mutations. Results: Among the 4,091 NSCLC patients, 2,411 (58.9%) experienced EGFR mutations. In which we identified 90 patients(2.2%) with Ex20ins. All of the Ex20ins were localized between amino acids S767-V774, and after C-helix of the EGFR kinase domain. Different from the exon 19 deletion, we found that Ex20ins exhibits various types of mutations. A total of 34 Ex20ins types were detected, with the most common A767_V769dupASV and S768_D770dupSVD mutations, accounting for 26% and 22.2% respectively. In addition, H773dupH (6.67%), H773_V774dupHV(5.56%), H773_V774insAH (2.22%), D770_N771insG (2.22%), and N771_P772insG(2.22%) were also observed in the NSCLC patients. Conclusions: We described the landscape of EGFR Ex20ins in Chinese NSCLC patients cohort. Based on the large sample size, the frequency of the Ex20ins mutation in Chinese NSCLC patients was 2.2%, and the types of EGFR Ex20ins mutation were highly heterogeneous. Citation Format: shun xu, Zhichao Fu. The landscape of EGFR exon 20 insertion mutations in Chinese patients with non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5838.

Background: Many patients with cancer have benefited from immunotherapy represented by the blockade of immune checkpoint PD-1/PD-L1. However, about 4-29% of cancer patients treated with immunotherapy developed hyper-progressive diseases(HPD) with accelerated tumor growth. MDM2/MDM4 amplification was suggested as genomic correlates for elevated risk hyperprogression. The objective of this study was to evaluate the frequency of amplification of MDM2/MDM4 in the Chinese solid tumor patients and to provide advice on the selecting of optimal treatment decisions. Methods: Tumor or blood samples were collected from 2,937 patients with solid cancer, genetic mutations and amplification was detected using the next-generation sequencing(NGS). Results: A total 112 patients with MDM2/MDM4 amplification were identified, including lung cancer 50.9% (57/112), colorectal cancer 14.3% (16/112), gastric cancer 8.0% (9/112), liver cancer 5.4% (6/112), Biliary tract cancers 4.5% (5/112), breast cancer 2.7% (3/112), and pancreatic ductal adenocarcinoma 2.7% (3/112). TMB value was identified, The median TMB for lung cancer was 9.13 mutations/Mb, median TMB for colorectal cancer was 13.8 mutations/Mb, a high TMB value in gastric cancer (median TMB=20.22 mutations/Mb), and median TMB for liver cancer was 17.9 mutations/Mb. Meanwhile, MSI was detected in 8% of patients with MDM2/MDM4 amplification, of which 3 in lung cancer, 5 in colorectal cancer, and 1in gastric cancer. Conclusions: Although amplification of MDM2/MDM4 was observed only in a small proportion of patients, it demonstrated an association with high TMB in several common cancer types. In addition, our data indicate that amplification of MDM2/MDM4 in different types of cancer is heterogeneous and that an appropriate immunotherapy strategy for patients with solid cancer should be noted. Citation Format: xiangyu sun, Zhichao Fu. A comprehensive pan-cancer analysis of MDM2/MDM4 gene amplification in Chinese solid cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5844.

Background: Gene fusion is one of the common types of pathogenic mutation in non-small cell lung cancer(NSCLC). Numerous fusion genes have been identified as important biomarkers and therapeutic targets in NSCLC. The identification and analysis of fusion genes will provide important insights into the mechanisms of NSCLC development and devise novel therapeutic strategies. Here, our primary objective was to describe the landscape of fusion in Chinese patients with NSCLC to explore the new treatment option in NSCLC. Methods: A total of 1192 pathologically confirmed NSCLC samples were collected. The fusion genes were detected using next-generation sequence(NGS). Results: A total of 168 fusion events (14.1%) were identified in 1,192 patients with NSCLC. The most common type of fusion was ALK (64.9%), RET (25%), ROS (8.93%), NTRK1 (3.57%), and FGFR3 (3.57%). In these cases, 109 patients exhibited ALK fusion, including EML4/ALK (97.2%), KIF5B/ALK (0.92%), KLC1/ALK (0.92%), and STRN/ALK (0.92%). A total of 42 patients had RET fusions, of which 83.3%, 11.9%, 2.38%, and 2.38% with KIF5B, CCDC6, GOPC, and TET1 respectively. Notably, RET gene fusions with GOPC (GOPC/RET1), TET1 (TET1/RET1) were first reported in NSCLC and the two novel fusions retained the complete kinase domain of RET. We also found three types of ROS fusions in 15 patients, CD74/ROS1(66.7%) and EZR/ROS1(20%) were the common fusions. Additionally, a new fusion LRIG3/ROS1 which retained the complete kinase domain was identified for the first time in NSCLC patients. Conclusions: We conducted a comprehensive review of fusion genes in Chinese patients with NSCLC. With the exception of common gene fusions, we found three cases of rare fusion mutations, which help to understand the potential pathogenic mechanisms of NSCLC and translate into therapeutic applications. Citation Format: qiuju lin, Zhichao Fu. The fusion gene landscape in Chinese patients with non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5845.

Objective: To explore the effectiveness and safety of apatinib in patients with malignant glioma. Methods: This is a retrospective case-control study in a single center. Patients with new postoperative pathological diagnosis of malignant glioma (WHO Ⅲ~Ⅳ) were selected. Enrolled patients received concurrent chemoradiotherapy (60Gy/30f/6w; TMZ75mg/m2,po,d1-d42)combined with or without apatinib (250mg, po, d1-d42,qd), then maintain 6 cycles(28 days a cycle)of TMZ chemotherapy(200mg/m2, d1-d5) .The primary endpoints were progression free survival (PFS) and the grade of peritumoral brain edema (PTBE) evaluated by edema index(EI). The secondary endpoint was overall survival(OS). Hazard ratios of PFS and OS were compared between trials in a Cox proportional hazards model.Results: 48 patients (24 in apatinib group and 24 in control group) were enrolled in this study. The results elucidated that the mPFS of the apatinib group was longer than control group, but the difference was not statistically significant(9.63 vs. 7.33 months; P=0.073).As for mOS, the results of two groups were almost similar.(15.47 vs. 14.70 months, P=0.612). Cox multivariate regression model revealed that Apatinib was not a prognostic factor for PFS and OS (P>0.05). Multivariate analysis showed that tumor grade was an important risk factor for PFS and OS.The grade of PTBE was improved in 15 of 23 patients (65.2%) in apatinib group versus 6 of 24 (25%) in control group. There was no grade 3 or 4 adverse events and serious adverse events.Conclusion: Apatinib group can improve mPFS by 2.3 months in patients with malignant glioma,but there was no statistical significance (P>0.05).The results also indicated that apatinib conferred a significant beneficial effect on PTBE improvement. All occurred adverse reactions were moderate and controllable.

Phase-locked loop (PLL) is commonly used for three-phase grid-connected inverters to obtain the information of grid synchronization, and PLL dynamics are the key factors for stable operation of the inverters. Under weak grid conditions, the coupling between PLL and grid impedance can result in harmonic resonance, or even instability in the system. In this paper, the effect of PLL dynamics and grid impedance on the stability of three-phase grid-connected inverters is studied with the d – q impedance model. Besides, the variable transfer relationship is used to analyze the influence of PLL perturbations on output current under weak grid conditions. To suppress low-order harmonics of the network current caused by PLL perturbations under weak grid conditions, a novel feedforward control method is proposed to compensate PLL perturbations and revise the output impedance, where the operation of the inverter and PLL dynamics have been taken into account in the design process. By analyzing the impedance characteristic of the system, it can be demonstrated that the proposed method can enhance the stability of grid-connected inverters under weak grid conditions and reduce the impact of PLL perturbations on grid-connecting current. The experimental results indicate that the low-order harmonics of the network current can be suppressed effectively, which verifies the analysis.

The accuracy of OCR is usually affected by the quality of the input document image and different kinds of marred document images hamper the OCR results. Among these scenarios, the low-resolution image is a common and challenging case. In this paper, we propose the cascaded networks for document image super-resolution. Our model is composed by the Detail-Preserving Networks with small magnification. The loss function with perceptual terms is designed to simultaneously preserve the original patterns and enhance the edge of the characters. These networks are trained with the same architecture and different parameters and then assembled into a pipeline model with a larger magnification. The low-resolution images can upscale gradually by passing through each Detail-Preserving Network until the final high-resolution images. Through extensive experiments on two scanning document image datasets, we demonstrate that the proposed approach outperforms recent state-of-the-art image super-resolution methods, and combining it with standard OCR system lead to signification improvements on the recognition results.

Being one of the most lethal cancers that exhibit high levels of heterogeneity, hepatocellular carcinoma (HCC) is associated with diverse oncogenic pathways underpinned by varied driver genes. HCC can be induced by different etiological factors including virus infection, toxin exposure or metabolic disorders. Consequently, patients may display varied genetic profiles, and may respond differently to the treatments involving inhibition of target pathways. These DNA/RNA mutations, copy number variations, chromatin structural changes, aberrant expression of non-coding RNAs and epigenetic modifications were considered as biomarkers in the application of precision medication. To explore how genetic testing could contribute to early diagnosis, prognosis, treatment and postoperative monitoring of HCC, we conducted a systematic review of genetic markers associated with different pathologies. Moreover, we summarized on-going clinical trials for HCC treatment, including the trials for multiple kinase inhibitors and immune checkpoint blockade (ICB). The efficacy of ICB treatment in HCC is not as good as what was observed in lung cancer and melanoma, which might be due to the heterogeneity of the microenvironment of the liver.

Proton exchange membrane fuel cell systems are widely used to drive vehicles. It is indispensable to establish accurate and simple control oriented model of the system. However, this control oriented model is difficult to build due to the characteristic of strongly nonlinear, coupled and time - varying in proton exchange membrane fuel cell systems. To solve this problem, nonlinear subspace identification method is proposed to discover linear parameter varying model for the proton exchange membrane fuel cell system. The modeling process can be divided into two stages. In the first stage, algebraic transformation method is proposed to transform the nonlinear model to linear parameter varying model. In the second stage, kernel method based subspace identification is presented to identify parameter matrices of the proton exchange membrane fuel cell system. The established model is demonstrated by a 50 kW on board proton exchange membrane fuel cell system under real driving condition. The results show that mean absolute percent error and root mean squared error are as low as 9.6941e−06 and 0.0957, respectively. Therefore, the control oriented model perfectly agrees with real data. Compared with the prediction error method and recursive neural network nonlinear auto - regressive moving average model with exogenous method, modeling accuracy and speed of the proposed method are the best. Moreover, linear control theory can be employed to design controller based on the linear parameter varying model, which greatly simplifies controller design for proton exchange membrane fuel cell systems.

The aim of the present study was to investigate the regulation of stromal cell‑derived factor 1 (CXCL12) in the radioresistance of cervical cancer, which was upregulated in tumors in our previous study. A CCK‑8 assay was used to detect cell viability. Flow cytometry was used to measure cell apoptosis and the expression levels of CD44 and CXCR4. ELISA was performed to measure the expression level of CXCL12 protein and CXCL12 mRNA was detected by reverse transcription‑quantitative polymerase chain reaction assays. Cell viability and apoptosis were determined with or without treatment with CXCL12 small interfering (si)RNA to examine the function of CXCL12 in Hela cells. The expression level of CD44 antigen (CD44) and C‑X‑C chemokine receptor type 4 (CXCR4) were measured using flow cytometry in the presence of CXCL12 and irradiation. In the present study, it was demonstrated that inhibition of CXCL12 reduced cell viability and increased cellular apoptosis in Hela cells treated with irradiation. Following treatment with CXCL12 siRNA, the expression level of CD44 was downregulated and the expression level of CXCR4 was upregulated. This effect of regulation additionally occurred in the presence of irradiation. In conclusion, the present data demonstrated that CXCL12 served an important role in the radioresistance of cervical cancer, suggestinh a novel therapeutic target.

The aim of the present study was to investigate the ability of bone marrow-derived mesenchymal stem cells (BMSCs) to repair radiation-induced acute intestinal injury, and to elucidate the underlying repair mechanism. Male Sprague-Dawley rats were subjected to whole abdominal irradiation using a single medical linear accelerator (12 Gy) and randomly assigned to two groups. Rats in the BMSC-treated group were injected with 1 ml BMSC suspension (2×106 cells/ml) via the tail vein, while the control group rats were injected with normal saline. BMSCs were identified by detecting the expression of CD29, CD90, CD34 and CD45 using flow cytometry. The expression of the cytokines stromal cell-derived factor 1 (SDF-1), prostaglandin E2 (PGE2) and interleukin (IL)-2 was detected using immunohistochemical techniques. Plasma citrulline concentrations were evaluated using an ELISA kit. Rat general conditions, including body weight, and changes in cellular morphology were also recorded. The results suggested that BMSCs exerted a protective effect on radiation-induced acute intestinal injury in rats. The histological damage was rapidly repaired in the BMSC-treated group. In addition, the BMSC-treated group showed significantly reduced radiation injury scores (P

The present study aimed to observe the role of mesenchymal stem cells (MSCs) in the repair of acute skin damage caused by radiation. Rat bone marrow MSCs (BMSCs) were isolated and cultured in vitro. A rat model of radiation‑induced acute skin damage was established by irradiation of the hind legs of Sprague-Dawley rats using a linear accelerator (45 Gy). After irradiation, rats were randomly divided into two groups: BMSC group and control group. Rats in the BMSC group were treated with a tail vein injection of 2x106 BMSCs (1 ml) immediately after irradiation and a local multipoint injection of 2x106 BMSCs at the injured area two weeks later. Then the wound healing of each rat was observed. The expression of transforming growth factor (TGF)‑β1, stromal cell‑derived factor-1 (SDF‑1) and prostaglandin E2 (PGE2) in the wounded tissues was determined by immunohistochemistry. The results demonstrated that skin damage was milder in the BMSC group than in the control group. Moreover, the speed of healing in the BMSC group was better than that in the control group. In addition, the wound score, it was significantly lower in the BMSC group than in the control group (P