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Abstract Objective Although health literacy (HL) has emerged as a critical public health concern, research on HL in emergency management departments is limited. This study aimed to investigate the awareness of HL and associated factors among firefighters of emergency management departments in southwest China to provide a basis for carrying out targeted health education. Methods A cross-sectional convenience sample of 1,742 firefighters from an emergency management department in southwestern China was surveyed from February to April 2023 using the Chinese Citizen’s Health Literacy Questionnaire (2019 version). The chi-square test, linear trend chi-square test, Fisher’s test, rank sum test, and multifactorial logistic regression model were used to identify influential factors associated with HL. Results The HL level of the 1742 respondents was 34.3%. Age, ethnicity, education level, length of service, type of job, smoking status, types of parental jobs, annual household income, time of daily internet use, etc. (P

Purpose: This systematic review and meta-analysis sought to assess whether ultra-high dose rate (UHDR) ion irradiations can induce the FLASH effect in animal models. Methods: A comprehensive search of the Web of Science, PubMed, and EMBASE databases was conducted from inception until March 20, 2023, to identify studies involving irradiated animals subjected to proton or carbon ion beams at varying dose rates. The research content should include various indicators that can reflect the effect and safety of radiation, such as survival, normal tissue toxicity, inflammatory response, tumor volume, etc Results: Compared to conventional dose rate (CONV) ion irradiations, UHDR ion irradiations can significantly improve mouse survival (HR 0.48, 95% CI 0.29 to 0.78, I 2 = 0%) and maintain comparable tumor control. There was no significant impact of different dose rates on the survival of zebrafish embryos (SMD 0.11, 95% CI −0.31 to 0.53, I 2 = 85%). Subgroup analysis showed that radiation dose was an important factor affecting the survival of zebrafish embryos. Achieving normal tissue sparing may require higher radiation dose under UHD.In mouse and zebrafish embryo models, normal tissue sparing did not always occur after UHDR ion irradiations. In addition, only a limited number of cytokines (CXCL1, IL-6, GM-CSF, G-CSF, HMGB1, and TGF-β) and immune cells (microglia and myeloid cells) showed differences at different dose rates. Conclusions: UHDR ion irradiation can achieve FLASH effect, but the reproducibility of normal tissue sparing remains a challenge. Compared to CONV irradiation, UHDR ion irradiations demonstrated equivalent or even superior tumor control.

On January 23，2024 at 02:09 (Beijing time), the MS7.1 earthquake occurred in Wushi county, Aksu Prefecture, Xinjiang. The Institute of Geophysics, China Earthquake Administration initiated a rapid response after the earthquake, organized researchers in related fields to estimate the source parameters, seismic radiation energy, and repositioned the aftershock sequence. At the same time, seismic map simulation and co-seismic deformation field simulation were carried out based on the source model. The results indicate that the earthquake occurred within the Tianshan Mountains, mainly through a thrust mechanism, with energy concentrated and released within the first 25 seconds; The seismic intensity in the extreme earthquake zone may reach over Ⅸ degrees, with a possible disaster area of nearly 65000 km2; This earthquake caused significant coseismic displacement, with a maximum horizontal displacement of 21 cm and a vertical displacement of 38 cm.

Abstract Background Primary thyroid lymphoma (PTL) is a rare malignant disorder, and ultrasound plays an important role in PTL diagnosis and follow-up surveillance. Prediction of refractory/relapse events in PTL patients is an essential issue, yet no ultrasonic PTL features have been discovered to be related to refractory/local relapse events. Methods From January 2008 to September 2022, newly diagnosed PTL patients in our center who underwent standard first-line treatment and received an ultrasound examination before treatment were enrolled. Data regarding patients’ clinical and sonographic features, as well as their therapeutic responses were collected. Subjects with an ideal prognosis were compared to those with refractory/relapse events. Results In total, 37 PTL patients were analyzed, including 26 with diffuse large B-cell lymphoma, 2 with follicular lymphoma and 9 with mucosa-associated lymphoid tissue lymphoma. During the median follow-up of 25 months, 30 patients obtained a complete response, 4 were refractory patients, and 3 experienced local relapse. No significant difference was detected in the baseline clinical characteristics between patients with an ideal prognosis and those with refractory/local relapse events. In terms of sonographic features, however, an event-free survival (EFS) curve comparison revealed that patients with bilobar enlargement (defined as an anterior-posterior diameter > 2.5 cm on both sides of thyroid lobes) had a poorer EFS than those without (P 2.5 cm for both thyroid lobes or PTL patients of the diffuse ultrasound type could be prone to refractory/local relapse events.

At 22:37 on December 2, 2023 (Beijing time), a M7.6 earthquake occurred in the eastern waters of Mindanao，Philippines. The Institute of Geophysics, China Earthquake Administration initiated the response mechanism after this earthquake and organized geophysics researchers to estimate the source parameters, focal mechanism，rupture process and earthquake radiation energy of this earthquake. Based on the source model, the Shakemap and the coseismic deformation field simulation are carried out. Product results demonstrate that this earthquake occurred on the subduction zone slab where the Philippine Sea Plate collided with the Eurasian Plate/Sunda Block. This earthquake is of dominant thrusting mechanism. The energy was concentrated and released in the first 40 seconds. The maximum slip of the fault rupture is up to 7 m. The efficiency of the earthquake source in radiating seismic energy is low and the slowness coefficient is slightly lower than the average level of the global same moment magnitude earthquake, and the feeling of the earthquake is relatively weak. The earthquake intensity in the extreme seismic area possibly reaches more than Ⅸ, and the approximate disaster range is up to 27000 km2. This earthquake caused apparent coseismic displacement with the maximum displacements reaching 0.6 m and 1.2 m in the horizontal and vertical directions respectively. Comprehensive analysis shows that this earthquake can’t produce a large-scale tsunami.

At 23:59 on December 18, 2023 (Beijing time), a M6.2 earthquake occurred in the Gansu Province of Jishishan. The Institute of Geophysics，China Earthquake Administration initiated the response mechanism after this earthquake and organized geophysics researchers to estimate the source parameters, focal mechanism, rupture process, earthquake radiation energy and earthquake relocation of this earthquake. Based on the source model, the Shakemap and the coseismic deformation field simulation are carried out. The results demonstrate that the earthquake is of dominant thrusting mechanism. The energy was concentrated and released in the first 8 seconds. The earthquake intensity in the extreme seismic area possibly exceeded Ⅷ, resulting in an estimated disaster range of approximately 6000 km2. This earthquake caused apparent horizontal coseismic displacement with maximum displacements reaching 7.8 cm and 15.8 cm.

The precise and automated diagnosis of apple leaf diseases is essential for maximizing apple yield and advancing agricultural development. Despite the widespread utilization of deep learning techniques, several challenges persist: (1) the presence of small disease spots on apple leaves poses difficulties for models to capture intricate features; (2) the high similarity among different types of apple leaf diseases complicates their differentiation; and (3) images with complex backgrounds often exhibit low contrast, thereby reducing classification accuracy. To tackle these challenges, we propose a three-residual fusion network known as MSCR-FuResNet (Fusion of Multi-scale Feature Extraction and Enhancements of Channels and Residual Blocks Net), which consists of three sub-networks: (1) enhancing detailed feature extraction through multi-scale feature extraction; (2) improving the discrimination of similar features by suppressing insignificant channels and pixels; and (3) increasing low-contrast feature extraction by modifying the activation function and residual blocks. The model was validated with a comprehensive dataset from public repositories, including Plant Village and Baidu Flying Paddle. Various data augmentation techniques were employed to address class imbalance. Experimental results demonstrate that the proposed model outperforms ResNet-50 with an accuracy of 97.27% on the constructed dataset, indicating significant advancements in apple leaf disease recognition.

Purposes To verify the axil fensile beaning performance of pre embeded mechanical sleeve connectors used for anti-pulling pile. Methods The axial tension test of 6 groups of anti-pulling pile tensile mechanical sleeve connectors was completed, and the maximum failure load and failure mode were obtained. Combined with the finite element calculation results, the stress distribution law of the specimen was analyzed to find out the stress concentration point or weak part. Findings The results show that the pre-embedded mechanical sleeve connection specimen meets the requirements of tensile bearing capacity; when the specimen was subjected to ultimate failure, the main failure phenomena were the failure of sleeve groove and steel bar end block; the inclination angle decrease of the contact surface between the pier head and the groove has a significant effect on improving the stress concentration of the specimen, it is suggested that the inclination angle should be controlled within 15°. Conclusion Pile concrete limits the deformation of sleeve connectors and improves the safety and reliability of specimens during pullout.

Abstract The degenerative process in Parkinson’s disease (PD) causes a progressive loss of dopaminergic neurons (DaNs) in the nigrostriatal system. Resolving the differences in neuronal susceptibility warrants an amenable PD model that, in comparison to post-mortem human specimens, controls for environmental and genetic differences in PD pathogenesis. Here we generated high-quality profiles for 250,173 cells from the substantia nigra (SN) and putamen (PT) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian macaques and matched controls. Our primate model of parkinsonism recapitulates important pathologic features in nature PD and provides an unbiased view of the axis of neuronal vulnerability and resistance. We identified seven molecularly defined subtypes of nigral DaNs which manifested a gradient of vulnerability and were confirmed by fluorescence-activated nuclei sorting. Neuronal resilience was associated with a FOXP2-centered regulatory pathway shared between PD-resistant DaNs and glutamatergic excitatory neurons, as well as between humans and nonhuman primates. We also discovered activation of immune response common to glial cells of SN and PT, indicating concurrently activated pathways in the nigrostriatal system. Our study provides a unique resource to understand the mechanistic connections between neuronal susceptibility and PD pathophysiology, and to facilitate future biomarker discovery and targeted cell therapy.

Abstract Objective Carbon ion radiotherapy (C-ion RT) for chordomas has been gradually performed in several research centres. This study aimed to systematically review the results of clinical reports from these institutions and to evaluate the safety and efficacy of C-ion RT. Methods In accordance with the PRISMA guidelines and set search strategies, we searched four databases for articles from their inception to February 11, 2023. These articles were screened, and data were extracted independently by two researchers. STATA 14.0 was used for statistical analysis of survival results. Results A total of 942 related articles were retrieved, 11 of which were included. Regarding lesion location, 57% (n = 552) originated in the sacral region, 41% (n = 398) in the skull base, and 2% (n = 19) in the spine (upper cervical). The local control (LC) rates at 1, 2, 3, 5, 9, and 10 years in these studies were 96%, 93%, 83%, 76%, 71%, and 54%, respectively. The overall survival (OS) rates at 1, 2, 3, 5, 9, and 10 years in these studies were 99%, 100%, 93%, 85%, 76%, and 69%, respectively. Acute and late toxicities were acceptable, acute toxicities were mainly grade 1 to grade 2 and late toxicities were mainly grade 1 to grade 3. Conclusion C-ion RT has attractive clinical application prospects and is an important local treatment strategy for chordomas. Encouraging results were observed in terms of LC and OS. Meanwhile, the acute and late toxicities were acceptable. PROSPERO registration number: CRD42023398792.

Camellia oleifera is a crop of high economic value, yet it is particularly susceptible to various diseases and pests that significantly reduce its yield and quality. Consequently, the precise segmentation and classification of diseased Camellia leaves are vital for managing pests and diseases effectively. Deep learning exhibits significant advantages in the segmentation of plant diseases and pests, particularly in complex image processing and automated feature extraction. However, when employing single-modal models to segment Camellia oleifera diseases, three critical challenges arise: (A) lesions may closely resemble the colors of the complex background; (B) small sections of diseased leaves overlap; (C) the presence of multiple diseases on a single leaf. These factors considerably hinder segmentation accuracy. A novel multimodal model, CNN–Transformer Dual U-shaped Network (CTDUNet), based on a CNN–Transformer architecture, has been proposed to integrate image and text information. This model first utilizes text data to address the shortcomings of single-modal image features, enhancing its ability to distinguish lesions from environmental characteristics, even under conditions where they closely resemble one another. Additionally, we introduce Coordinate Space Attention (CSA), which focuses on the positional relationships between targets, thereby improving the segmentation of overlapping leaf edges. Furthermore, cross-attention (CA) is employed to align image and text features effectively, preserving local information and enhancing the perception and differentiation of various diseases. The CTDUNet model was evaluated on a self-made multimodal dataset compared against several models, including DeeplabV3+, UNet, PSPNet, Segformer, HrNet, and Language meets Vision Transformer (LViT). The experimental results demonstrate that CTDUNet achieved an mean Intersection over Union (mIoU) of 86.14%, surpassing both multimodal models and the best single-modal model by 3.91% and 5.84%, respectively. Additionally, CTDUNet exhibits high balance in the multi-class segmentation of Camellia oleifera diseases and pests. These results indicate the successful application of fused image and text multimodal information in the segmentation of Camellia disease, achieving outstanding performance.

Abstract Background The early diagnosis of medullary thyroid carcinoma (MTC) is still a challenge in clinical practice. Based on ultrasound features, many MTC cases without suspicious characteristics are not categorized as high risk for malignancy. This study was designed to comprehensively investigate the ultrasonic features of MTC on ultrasound and help identify thyroid nodules with a high risk of MTC. Methods Between 2017 and 2023, we retrospectively reviewed 116 consecutive thyroid nodules with a histologic diagnosis of MTC who had undergone preoperative ultrasound examination. According to the ultrasonic criteria for risk classification, nodules were classified as “ultrasound-high suspicious” (h-MTC) and “ultrasound-low suspicious” (l-MTC). Using the same database, a tumour size- and risk evaluation-matched control group comprising 62 lesions was randomly selected to compare the vascularity features of l-MTC disease. Results We identified 85 h-MTC nodules (73.3%) and 31 l-MTC nodules (26.7%). For patients with l-MTC disease, 22/31 (71.0%) of the lesions were followed up for a period before fine needle aspiration (FNA) or surgery. We observed more penetrating branching vascularity in the l-MTC group than in the benign nodule group (23/31, 74.2% vs. 5/59, 4.8%, P

Toxidromes constitute patterns of symptoms and signs caused by specific toxic effects that guide emergency treatments. Computational identification of chemicals that cause different toxidromes allows us to rapidly screen novel compounds and compound classes as to their potential toxicity. The aim of the current study was to create a computational toolset that can map chemicals to their potential toxidromes. Hence, we evaluated the performance of a state-of-the-art deep learning method—the recently developed communicative message passing neural network (CMPNN)—for its ability to overcome the use of small datasets for training deep learning models. Our results indicated that multi-task training—a technique known for its ability to use multiple small datasets to train conventional deep neural networks—works equally well with CMPNN. We also showed that CMPNN-based ensemble learning results in more reliable predictions than those obtained using a single CMPNN model. In addition, we showed that the standard deviations of individual model predictions from an ensemble of CMPNN models correlated with the errors of ensemble predictions and could be used to estimate the reliability of ensemble predictions. For toxidromes that do not have well-defined molecular mechanisms or sufficient data to train a deep learning model, we used the similarity ensemble approach to develop molecular structural similarity-based toxidrome models. We made the toolset developed in this study publicly accessible via a web user interface at https://toxidrome.bhsai.org/.

Abstract Background and purpose Particle therapy, mainly including carbon-ion radiotherapy (CIRT) and proton beam therapy (PBT), has dose distribution advantages compared to photon radiotherapy. It has been widely reported as a promising treatment method for early non-small cell lung cancer (NSCLC). However, its application in locally advanced non-small cell lung cancer (LA-NSCLC) is relatively rare, and its efficacy and safety are inconclusive. This study aimed to provide systematic evidence for evaluating the efficacy and safety of particle therapy for inoperable LA-NSCLC. Methods To retrieve published literature, a systematic search was conducted in PubMed, Web of Science, Embase, and Cochrane Library until September 4, 2022. The primary endpoints were local control (LC) rate, overall survival (OS) rate, and progression-free survival (PFS) rate at 2 and 5 years. The secondary endpoint was treatment-related toxicity. The pooled clinical outcomes and 95% confidence intervals (CIs) were calculated by using STATA 15.1. Results Nineteen eligible studies with a total sample size of 851 patients were included. The pooled data demonstrated that the OS, PFS, and LC rates at 2 years of LA-NSCLC treated by particle therapy were 61.3% (95% CI = 54.7-68.7%), 37.9% (95% CI = 33.8-42.6%) and 82.2% (95% CI = 78.7-85.9%), respectively. The pooled 5-year OS, PFS, and LC rates were 41.3% (95% CI = 27.1-63.1%), 25.3% (95% CI = 16.3-39.4%), and 61.5% (95% CI = 50.7-74.6%), respectively. Subgroup analysis stratified by treatment type showed that the concurrent chemoradiotherapy (CCRT, PBT combined with concurrent chemotherapy) group had better survival benefits than the PBT and CIRT groups. The incidence rates of grade 3/4 esophagitis, dermatitis, and pneumonia in LA-NSCLC patients after particle therapy were 2.6% (95% CI = 0.4-6.0%), 2.6% (95% CI = 0.5-5.7%) and 3.4% (95% CI = 1.4-6.0%), respectively. Conclusions Particle therapy demonstrated promising efficacy and acceptable toxicity in LA-NSCLC patients.

Background: Gliomas are characterized by aggressive behavior, leading to severe disability and high mortality. Ubiquitin-like modifier activating enzyme 2 (UBA2) is a subunit of the E1-activating enzyme involved in the SUMOylation (SUMO, small ubiquitin-related modifier) of numerous proteins. Although the abnormality of UBA2 is linked to the progression of various tumor types, the role of UBA2 in glioma is still unknown. Methods: A bioinformatic analysis using several public databases was conducted to examine the expression level, clinicopathological correlations, and prognostic significance of UBA2 in glioma. The correlation between UBA2 expression and drug sensitivity in cancers was also explored. Multiple cellular experiments were conducted to validate the role of UBA2 in glioma. Results: Analysis of multiple databases and cellular experiments revealed that UBA2 was overexpressed in glioma tissues and cell lines, respectively. UBA2 expression in gliomas correlated with World Health Organization (WHO) grade, IDH gene status, 1p19q deletion, histological type, and immune cell infiltration in glioma. UBA2 expression in carcinomas also correlated with drug sensitivity. Kaplan-Meier analysis revealed that high expression of UBA2 predicted poorer survival in glioma patients. A nomogram model containing UBA2 expression was constructed for clinical practice. Knockdown of UBA2 was observed to suppress glioma cell progression and sensitize glioma cells to irradiation in vitro. Conclusion: Overall, this research showed that UBA2 might be involved not only in the development of glioma but also in the regulation of immunity, drug sensitivity, and radiosensitivity. Therefore, UBA2 may be a potential target for therapy and a candidate biomarker for glioma diagnosis and prognosis.

Abstract Objective This study aimed to evaluate and conduct a meta-analysis on the efficacy and safety of proton beam therapy (PBT) for rhabdomyosarcoma (RMS). Methods We searched for articles using PubMed, Embase, Cochrane Library, and Web of Science databases from their inception to December 22, 2022. Two researchers independently screened literature and extracted data. Statistical analyses were performed using STATA version 14.0. Results We got 675 candidate articles, of which 11 studies were included in our study according to the inclusion and exclusion criteria. Of the 544 RMS patients who received PBT. The local control (LC) rate at 1, 2, 3, 4, and 5 years were 96% (95% confidence interval (CI) 0.91–1.01), 93% (95% CI 0.86–1.00), 78% (95% CI 0.71–0.85), 85% (95% CI 0.78–0.92), and 84% (95% CI 0.74–0.95), respectively. The progression-free survival (PFS) rate at 1, 2, 3, 4, and 5 years were 82% (95% CI 0.72–0.92), 73% (95% CI 0.61–0.84), 63% (95% CI 0.47–0.79), 64% (95% CI 0.54–0.74), and 76% (95% CI 0.59–0.94), respectively. The overall survival (OS) rate at 1, 2, 3, 4, and 5 years were 93% (95% CI 0.86–1.00), 85% (95% CI 0.76–0.95), 80% (95% CI 0.63–0.96), 71% (95% CI 0.62–0.80), and 82% (95% CI 0.71–0.94), respectively. Acute and late toxicities were mainly grades 1 to 2 in all studies. Conclusion As an advantageous RT technique, PBT is an emerging option for patients with RMS, particularly children and adolescents patients. The data showed that PBT is a feasible, safe, and effective modality for RMS, showing promising LC, OS, PFS, and lower acute and late toxicities. PROSPERO registration number: CRD42022329154.

Abstract High-grade gliomas are the most common intracranial malignancies, and their current prognosis remains poor despite standard aggressive therapy. Charged particle beams have unique physical and biological properties, especially high relative biological effectiveness (RBE) of carbon ion beam might improve the clinical treatment outcomes of malignant gliomas. We systematically reviewed the safety, efficacy, and dosimetry of carbon-ion or proton radiotherapy to treat high-grade gliomas. The protocol is detailed in the online PROSPERO database, registration No. CRD42021258495. PubMed, EMBASE, Web of Science, and The Cochrane Library databases were collected for data analysis on charged particle radiotherapy for high-grade gliomas. Until July 2022, two independent reviewers extracted data based on inclusion and exclusion criteria. Eleven articles were eligible for further analysis. Overall survival rates were marginally higher in patients with the current standard of care than those receiving concurrent intensity-modulated radiotherapy plus temozolomide. The most common side effects of carbon-ion-related therapy were grade 1–2 (such as dermatitis, headache, and alopecia). Long-term toxicities (more than three to six months) usually present as radiation necrosis; however, toxicities higher than grade 3 were not observed. Similarly, dermatitis, headache, and alopecia are among the most common acute side effects of proton therapy treatment. Despite improvement in survival rates, the method of dose-escalation using proton boost is associated with severe brain necrosis which should not be clinically underestimated. Regarding dosimetry, two studies compared proton therapy and intensity‐modulated radiation therapy plans. Proton therapy plans aimed to minimize dose exposure to non-target tissues while maintaining target coverage. The use of charged-particle radiotherapy seems to be effective with acceptable adverse effects when used either alone or as a boost. The tendency of survival outcome shows that carbon ion boost is seemingly superior to proton boost. The proton beam could provide good target coverage, and it seems to reduce dose exposure to contralateral organs at risk significantly. This can potentially reduce the treatment-related dose- and volume-related side effects in long-term survivors, such as neurocognitive impairment. High-quality randomized control trials should be conducted in the future. Moreover, Systemic therapeutic options that can be paired with charged particles are necessary.

zong non-coding RNAs (lncRNAs) have been identified as crucial effector in modulating the progression of assorted malignancies. In our study, the main aim was to unveil the role and the underlying regulatory mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in nasopharyngeal carcinoma (NPC). RT-qPCR analysis results suggested that LINC01605 was upregulated in NPC cells. According to the results of function experiments, LINC01605 promoted NPC cell proliferation and impeded cell apoptosis. The oncogenic role of LINC01605 in NPC was further validated by animal experiments. Additionally, we verified that LINC01605 regulated Ikbkb expression to promote the nuclear translocation of p65 and thereby activated the NF-κB pathway in NPC cells. Mechanism experiments further suggested that LINC01605 could regulate Ikbkb expression via sponging miR-942-5p. Moreover, LINC01605 recruited IGF2BP2 to stabilize ubiquitin-specific protease 3 (USP3) mRNA and thereby enhanced the stability of IkB subunit beta (IKKβ) protein. In addition, p65 acted as a transcription activator to upregulate LINC01605 in NPC cells. In conclusion, this study demonstrated a positive feedback loop between LINC01605 and the NF-κB signalling pathway that promoted NPC cell growth, thus providing new insights to better understand NPC.

Abstract Background Charged particle beams from protons to carbon ions provide many significant physical benefits in radiation therapy. However, preclinical studies of charged particle therapy for prostate cancer are extremely limited. The aim of this study was to comprehensively investigate the biological effects of charged particles on prostate cancer from the perspective of in vitro studies. Methods We conducted a systematic review by searching EMBASE (OVID), Medline (OVID), and Web of Science databases to identify the publications assessing the radiobiological effects of charged particle irradiation on prostate cancer cells. The data of relative biological effectiveness (RBE), surviving fraction (SF), standard enhancement ratio (SER) and oxygen enhancement ratio (OER) were extracted. Results We found 12 studies met the eligible criteria. The relative biological effectiveness values of proton and carbon ion irradiation ranged from 0.94 to 1.52, and 1.67 to 3.7, respectively. Surviving fraction of 2 Gy were 0.17 ± 0.12, 0.55 ± 0.20 and 0.53 ± 0.16 in carbon ion, proton, and photon irradiation, respectively. PNKP inhibitor and gold nanoparticles were favorable sensitizing agents, while it was presented poorer performance in GANT61. The oxygen enhancement ratio values of photon and carbon ion irradiation were 2.32 ± 0.04, and 1.77 ± 0.13, respectively. Charged particle irradiation induced more G0-/G1- or G2-/M-phase arrest, more expression of γ-H2AX, more apoptosis, and lower motility and/or migration ability than photon irradiation. Conclusions Both carbon ion and proton irradiation have advantages over photon irradiation in radiobiological effects on prostate cancer cell lines. Carbon ion irradiation seems to have further advantages over proton irradiation. Graphical Abstract

There are a series of complex physical phenomena in once-through steam generators (OTSG), such as full-regime flow boiling and phase-change heat transfer from supercooled water to superheated steam, coupled heat transfer between tube side and shell side. At the same time, the structure of OTSG is also very complex. There are a large number of slender heat exchange tubes in the OTSG, and the difference between the radial size and the axial size is very large, that is, the size span is large. These problems and characteristics lead to the problems of high computational difficulty, low solution efficiency and poor solution stability when using computational fluid dynamics (CFD) and threedimensional refined modeling methods to analyze the three-dimensional temperature field of OTSG with large-scale heat exchange tube bundles. Based on the full-regime flow boiling, phase-change heat transfer model and the criterion model of boiling flow regime, a one-dimensional full-regime flow boiling and phase-change heat transfer analytical model were stablished in this paper. With appropriate parameter transfer, the cross-scale coupling solution between the one-dimensional boiling heat transfer analytical model on the tube side and the three-dimensional refined CFD model on the shell side was realized. This crossscale coupling calculation method can realize the independent coupling between each heat exchange tube on the water side and the threedimensional fluid domain on the sodium side. The proposed crossscale coupling numerical model was applied to the oncethrough steam generator of the Indian fast reactor to realize the independent coupling between each OTSG heat exchange tube and the shell side threedimensional sodium fluid domain, and the plugged tube condition analyses were carried out. The effectiveness of the proposed cross-scale coupling model was verified by comparison with experimental data. The study results show that the established crossscale coupling numerical analysis model between tube side and shell side can accurately predict the temperature distribution and the main heat transfer characteristic points of each heat exchange tube over the entire height. The calculation results can also give the temperature of different heat exchange tubes and the temperature difference between the tube walls of each heat exchange tube in detail. This method is also very convenient to realize the analysis of plugging conditions. The crossscale coupling solution method avoids the direct solution of complex threedimensional multiphase flow equations, and greatly improves the efficiency and stability of the numerical solution of the OTSG threedimensional temperature field. This study provides an efficient threedimensional refined analysis method for the design and safety verification of OTSG.

Abstract Objective Parathyroid carcinoma (PC) and atypical parathyroid tumor (APT) are rare parathyroid disorders carrying the risk of recurrence of varying degrees. This study aims to explore the value of 2D-shear wave elastography (SWE) in the discrimination of PC/APT among suspicious parathyroid lesions. Methods and materials In this prospective study, patients with primary hyperparathyroidism and suspicious parathyroid lesions on ultrasonography (US) were recruited. All the lesions were assessed by SWE before surgery. The velocity (m/s), Young’s modulus (Kpa), and elastogram of SWE were compared between pathologically proven parathyroid carcinoma or atypical parathyroid tumor (Group1) and parathyroid adenoma (Group2). All the SWE parameters were displayed at the setting of 50 or 70 kPa. Correlations between SWE and the lesion size as well as biochemical parameters were analyzed. Results 36 target lesions were enrolled for analysis. The mean shear wave velocity (SWV) between the two groups was 2.4 m/s vs 1.9 m/s, respectively, while the mean Young’s modulus was 11.1 kPa vs 18.2 kPa, respectively. The cut-off values are 2.35 m/s and 17.05 kPa correspondingly. The sensitivity and specificity of the selecting cut-off values were 0.56 vs 0.63 and 0.95 vs 1.0 (area under the curve [AUC]: 0.813 vs 0.852 [95% confidence interval (CI): 0.669–0.956 vs 0.720–0.983]; p

Abstract The primate neocortex exerts high cognitive ability and strong information processing capacity. Here, we establish a single-cell RNA sequencing dataset of 133,454 macaque visual cortical cells. It covers major cortical cell classes including 25 excitatory neuron types, 37 inhibitory neuron types and all glial cell types. We identified layer-specific markers including HPCAL1 and NXPH4, and also identified two cell types, an NPY-expressing excitatory neuron type that expresses the dopamine receptor D3 gene; and a primate specific activity-dependent OSTN + sensory neuron type. Comparisons of our dataset with humans and mice show that the gene expression profiles differ between species in relation to genes that are implicated in the synaptic plasticity and neuromodulation of excitatory neurons. The comparisons also revealed that glutamatergic neurons may be more diverse across species than GABAergic neurons and non-neuronal cells. These findings pave the way for understanding how the primary cortex fulfills the high-cognitive functions.

Magnitude is a measure of the size of an earthquake. In practical work such as seismic activity analysis, people usually think that an earthquake has only one magnitude. Many people will have such doubts：why use multiple magnitudes? Why magnitude can’t be unified? In earthquake monitoring, why magnitudes can’t be converted to each other? Why are different magnitudes of the same earthquake different? How to use multiple magnitudes? This paper describes the principle of magnitude determination and the cleverness of magnitude, and discusses the above 11 problems so that scientific researchers and managers can correctly determine and use magnitude in practical work.

Abstract Objective This study aimed to systematically evaluate and conduct a meta-analysis of the efficacy and safety of carbon ion radiotherapy for bone sarcomas. Methods We searched for articles using the PubMed, Embase, Cochrane Library, and the Web of Science databases from their inception to January 12, 2022. Two researchers independently screened the literature and extracted data based on the inclusion and exclusion criteria. Statistical analyses were performed using STATA version 14.0. Results We searched for 4378 candidate articles, of which 12 studies were included in our study according to the inclusion and exclusion criteria. Of the 897 BSs patients who received carbon ion radiotherapy in the studies, 526 patients had chordoma, 255 patients had chondrosarcoma, 112 patients had osteosarcoma, and 4 patients had other sarcomas. The local control rate at 1, 2, 3, 4, 5, and 10 years in these studies were 98.5% (95% confidence interval [CI] = 0.961–1.009, I 2 = 0%), 85.8% (95% CI = 0.687–1.030, I 2 = 91%), 86% (95% CI = 0.763–0.957, I 2 = 85.3%), 91.1% (95% CI = 0.849–0.974), 74.3% (95% CI = 0.666–0.820, I 2 = 85.2%), and 64.7% (95% CI = 0.451–0.843, I 2 = 95.3%), respectively. The overall survival rate at 1, 2, 3, 4, 5, and 10 years in these studies were 99.9% (95% CI = 0.995–1.004, I 2 = 0%), 89.6% (95% CI = 0.811–0.980, I 2 = 96.6%), 85% (95% CI = 0.750–0.950, I 2 = 89.4%), 92.4% (95% CI = 0.866–0.982), 72.7% (95% CI = 0.609–0.844, I 2 = 95.3%), and 72.1% (95% CI = 0.661–0.781, I 2 = 46.5%), respectively. Across all studies, the incidence of acute and late toxicities was mainly grade 1 to grade 2, and grade 1 to grade 3, respectively. Conclusion As an advanced radiotherapy, carbon ion radiotherapy is promising for patients with bone sarcomas that are unresectable or residual after incomplete surgery. The data indicated that carbon ion radiotherapy was safe and effective for bone sarcomas, showing promising results for local control, overall survival, and lower acute and late toxicity. PROSPERO registration number CRD42021258480.

Three-dimensional rock fracture induced by blasting is a highly complex problem and has received considerable attention in geotechnical engineering. The material point method is firstly applied to treat this challenging task. Some inherent weaknesses can be overcome by coupling the generalized interpolation material point (GIMP) and the convected particle domain interpolation technique (CPDI). For the media in the borehole, unchanged GIMP-type particles are used to guarantee a homogenous blast pressure. CPDI-Tetrahedron type particles are employed to avoid the fake numerical fracture near the borehole for the rock material. A blasting experiment using three-dimensional single-borehole rock was simulated to examine the applicability of the coupled model under realistic loading and boundary conditions. A good agreement was achieved between the simulation and experimental results. Moreover, the mechanism of three-dimensional rock fracture was analyzed. It was concluded that rock particle size and material parameters play an important role in rock damage. The reflected tensile waves cause severe damage in the lower part of the model. Rayleigh waves occur on the top face of the rock model to induce a hoop failure band.

Radiotherapy is one of the main treatments for cervical cancer. Early cervical cancer is usually considered postoperative radiotherapy alone. Radiotherapy combined with cisplatin is the standard treatment for locally advanced cervical cancer (LACC), but sometimes the disease will relapse within a short time after the end of treatment. Tumor recurrence is usually related to the inherent radiation resistance of the tumor, mainly involving cell proliferation, apoptosis, DNA repair, tumor microenvironment, tumor metabolism, and stem cells. In the past few decades, the mechanism of radiotherapy resistance of cervical cancer has been extensively studied, but due to its complex process, the specific mechanism of radiotherapy resistance of cervical cancer is still not fully understood. In this review, we discuss the current status of radiotherapy resistance in cervical cancer and the possible mechanisms of radiotherapy resistance, and provide favorable therapeutic targets for improving radiotherapy sensitivity. In conclusion, this article describes the importance of understanding the pathway and target of radioresistance for cervical cancer to promote the development of effective radiotherapy sensitizers.

To reveal the seismogenic mechanism of the Luding earthquake, we employed the 118 China Seismic Network stations to collect the P-wave polarity data from each station, which was then used in the P-wave first motion approach to calculate the focal mechanism solution of the M6.8 Luding earthquake that occurred on September 5, 2022. We have also studied the loading effect of tectonic stress on the Luding earthquake fault based on the stress field data for the research area. The results indicate that this earthquake was a strike-slip type, the nodal plane I: strike 167°, dip Angle 78°, slip Angle 2°; Nodal plane Ⅱ: strike 77°, dip Angle 88°, slip Angle 168°. The two fault planes’ instability coefficients of the Luding earthquake are examined considering the region’s background stress field’s condition. The nodal plane I in the Moho circle is discovered to practically coincide with the Coulomb failure line and the tangent point of the Moho circle, indicating that this nodal plane has a high instability coefficient compared to the nodal plane II. The conclusion is that the nodal plane I has a higher likelihood of being the seismogenic fault plane, which is congruent with the seismogenic fault plane suggested by the aftershock distribution, the earthquake radiation energy distribution of a single station, and seismic intensity distribution. The Luding earthquake’s focal mechanism is highly like the theoretical focal mechanism of the fault situated at the location where the Coulomb failure line intersects the Mohr circle, demonstrating that background stress is what caused the earthquake. The substantial fault instability and similarity between the solved and theoretical focal mechanisms make it easier to comprehend the loading effect of tectonic stress on the Luding earthquake fault.

Purpose To identify candidate factors for predicting high-volume lateral lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC). Methods We retrospectively studied 2981 patients with PTMC who underwent thyroidectomy from 2013 to 2016. LLNM was identified by histopathology. Patients with different LLNM statuses were compared according to clinical, sonographic and pathological parameters. A multivariate logistic model was established to predict high-volume LLNM (number of metastatic lymph nodes >5). Results High-volume LLNM of PTMC was independently associated with age < 40 years (OR = 1.791, P = 0.023), male sex (OR = 2.401, p = 0.001), tumor size > 0.5 cm (OR = 4.839, p 0.5 cm, extrathyroidal extension and microcalcification were relatively higher than those without. These findings may be useful for identifying patients at higher high-volume LLNM risk who may require more aggressive treatment or intensive follow-up management.

Abstract Objective Carbon ions suppress the effect of glutathione peroxidase 4 (GPX4) on the proliferation and metastasis of lung adenocarcinoma A549 cells. Methods The clonogenic formation ability of A549 cells was calculated with different ray doses of radiation. Cell proliferation, cycle, and apoptosis of A549 cells after different ray irradiation were detected by cck8 and flow cytometry. The transwell assay was used to detect the cell migration and invasion after different rays of radiation to A549 cells. The GPX4 matrix metalloproteinase 2 and E‐cadherin expression levels were assessed by immunofluorescence and western blot. Results At the dose of 4 Gy, A549 cell viability was 22.95 ± 5.00% and 55.52 ± 3.26% when treated with carbon ions and X‐rays, respectively. The distribution of A549 cells arrested in the G2 phase by carbon ion irradiation was positively correlated with radiation dose, with a most significant increase at 4 Gy irradiation (t = 4.303, p

Abstract Background To explore the expression and carcinogenic mechanism of RIPK2 in human tumours, and to provide the theoretical basis for the further study of RIPK2. Methods We used the TCGA, CPTAC, HPA databases to analyse the expression, mutation, and prognosis of RIPK2 in human tumours. Through the Cbioportal, Ualcan, TIMER2.0, and STRING websites, We understand the genetic variation, immune infiltration and enrichment analysis of RIPK2 related genes. Results RIPK2 was highly expressed in most tumours (such as BRCA, COAD and LUSC, etc.), and the high expression of RIPK2 was correlated with tumour stage and prognosis. In addition, Amplification was the main type of RIPK2 in tumour mutation state, and the amplification rate was about 8.5%. In addition, RIPK2 was positively associated with tumour-infiltrating immune cells (such as CD8+ T, Tregs, and cancer-associated fibroblasts). According to the KEGG analysis, RIPK2 may play a role in tumour mainly through NOD-like signaling pathway and NF-kappaB signaling pathway. GO enrichment analysis showed that the RIPK2 is mainly related to I-kappaB kinase/NF-kappaB signaling, Ribonucleoprotein granule and Ubiquitin-like protein ligase binding. Conclusion RIPK2 plays an important role in the occurrence, development and prognosis of malignant tumours. Our pancancer study provided a relatively comprehensive description of the carcinogenic effects of RIPK2 in different tumours, and provided useful information for further study of RIPK2.

The irrational application of chemical fertilizer affects agricultural land’s supply capacity and yield quality and may lead to serious agricultural non-point source pollution. Through scientific and accurate fertilization, soil testing and formula fertilization technology (STFFT) can effectively prevent excessive fertilizer use, improve its utilization efficiency, and have significant environmental and economic benefits. Based on evolutionary game theory, this paper constructed an evolutionary game model of farmers’ adoption of STFFT. We used a case study to reveal and verify the influence of farmers’ environmental values, information awareness, and social network on their adoption of STFFT and its mechanism. The findings were as follows: First, there are two optimal stable states in the evolutionary system; namely, all farmers adopt or do not adopt STFFT. Second, environmental values and information awareness positively correlate with farmers’ adoption of STFFT. Third, the strength of social networks can enhance the effectiveness of information awareness and environmental values, encouraging farmers to adopt STFFT. In addition, the social network plays a mediating role and moderating role in the influence of information awareness and environmental values on the farmers’ adoption of STFFT.

After the occurrence of the 2008 Wenchuan Mw 7.9 earthquake, the Longmen-Shan fault zone exhibits highly active seismicity. In the years between 2008 and 2022, successive moderate magnitude aftershocks followed in the region. In this study, we used high-quality seismic data from the National Earthquake Data Center of China to estimate the source parameters of 184 moderate magnitude events (Mw 3.9–6.2) in the Longmen-Shan Fault zone. The dataset comprised the aftershocks of two sequences that occurred in the area, including the 2008 Wenchuan earthquake sequence and the 2013 Lushan earthquake sequence. They have been classified according to their focal mechanism. First, our results suggested that the values of apparent stress varied from approximately 0.1–11 MPa, which are higher than the global average. The strike-slip earthquakes have the highest average apparent stress among the types of earthquakes. The above results indicate that the moderately high levels of energy release from earthquakes in this region could result in high ground shaking potential. This behavior may be associated with the high stress accumulation and the strong deformation characteristics in the intraplate environment of the Longmen-Shan Fault zone. The values of the stress drop vary from approximately 0.24–39 MPa and appear to show a slightly increasing trend with the seismic moment. The stress drop level of the Lushan earthquake sequence is higher than the mean value of intraplate earthquakes, while the Wenchuan earthquake sequence is typical of intraplate earthquakes. Second, we investigate the radiated energy enhancement factor (REEF) to quantify the source complexities. The results show that the earthquakes have REEF values between 1.2 and 7.1, and most events are consistent with expectations based on the Brune ω-square model. There exist differences in the source complexity of earthquakes within the source area, and the average ω-square source model could result in an unreliable estimate of the radiated seismic energy of some events. The observation of moderate magnitude earthquakes suggests that the availability of different source parameters will help us to assess the seismic hazard and predict the shaking potential in the earthquake area.

Agriculture is a primary source of livelihoods in developing countries. The process of entry and exit of farming activities continues to play an important role in maintaining competition in agriculture and allocating resources between agriculture and other sectors. However, climate changes and other economic and social shocks have been severely affecting farmers’ livelihoods. This article examines rural household livelihood transition in the context of farm entry and exit decisions in rural Pakistan. Using 1867 rural household survey data, we brought insights into how livelihood assets, climate shocks, climate investment and locational characteristics affect their farm entry and exit decisions. The results indicate that the proportion of farm entry (24%) was higher than that of farm exit (15%). The major factors were crop inputs using as credit with a huge markup, crop inputs sold by farmers on net cash in financial crisis, climate shocks and poor climate investment that contributed to farm exit. They were household head characteristics, land ownership (family farm), and livestock ownership that increased the likelihood of farm entry decisions. Farm exit decisions were significantly and positively associated with household migration status, irrigation water shortage, off-farm income, crop input used as credit, crop diseases, climate shocks and lack of local government role in sharing climate knowledge. Furthermore, Propensity Score Matching (PSM) results found that the entry decision significantly decreases household income, while the exit decision significantly increases household income and food security status. These findings provide insights into farm entry and exit for those who are planning livelihood transition, and offer recommendations on how to overcome the constraints faced by farming businesses, agricultural sustainability, self-sufficiency and food security during the transition nationally and internationally.

Abstract Background and aims The existing evidence has indicated that hyperthermia ablation (HA) and HA combined with transarterial chemoembolization (HATACE) are the optimal alternative to surgical resection for patients with hepatocellular carcinoma (HCC) in the COVID‐19 crisis. However, the evidence for decision‐making is lacking in terms of comparison between HA and HATACE. Herein, a comprehensive evaluation was performed to compare the efficacy and safety of HATACE with monotherapy. Materials and Methods Worldwide studies were collected to evaluate the HATACE regimen for HCC due to the practical need for global extrapolation of applicative population. Meta‐analyses were performed using the RevMan 5.3 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). Results Thirty‐six studies involving a large sample of 5036 patients were included finally. Compared with HA alone, HATACE produced the advantage of 5‐year overall survival (OS) rate (OR:1.90; 95%CI:1.46,2.46; p 3 cm) HCC with comparable safety. However, the survival benefit of adjuvant TACE in HATACE regimen was not found for the patients with small (≤3 cm) HCC.

Abstract Background The lncRNA H19 is believed to act as an oncogene in various types of tumors and is considered to be a therapeutic target and diagnostic marker. However, the role of the lncRNA H19 in regulating the radiosensitivity of non-small cell lung cancer (NSCLC) cells is unknown. Methods The expression profiles of lncRNAs in NSCLC were explored via transcriptome sequencing. CCK-8, EdU incorporation and clonogenic survival assays were conducted to evaluate the proliferation and radiosensitivity of NSCLC cells. Flow cytometry and Western blotting were conducted to measure the level of apoptosis. The binding relationship between the lncRNA H19 and miR-130a-3p was determined by a dual-luciferase reporter assay. A binding relationship was also identified between miR-130a-3p and With-No-Lysine Kinase 3 (WNK3). Results Expression patterns of lncRNAs revealed that the lncRNA H19 was upregulated in radioresistant NSCLC (A549-R11) cells compared with A549 cells. Knockdown of the lncRNA H19 enhanced the sensitivity of NSCLC cell lines to X-ray and carbon ion irradiation. Mechanistically, the lncRNA H19 serves as a sponge of miR-130a-3p, which downregulates WNK3 expression. The lncRNA H19–miR-130a-3p–WNK3 axis modulates radiosensitivity by regulating apoptosis in NSCLC cell lines. Conclusion Knockdown of the lncRNA H19 promotes the sensitivity of NSCLC cells to X-ray and carbon ion irradiation. Hence, the lncRNA H19 might function as a potential therapeutic target that enhances the antitumor effects of radiotherapy in NSCLC.

BackgroundMost of coronary artery ectasia (CAE) patients have comorbid coronary atherosclerosis. It was lack of prognostic data for CAE patients with coronary heart disease (CHD) and for whom with acute myocardial infarction (AMI).ObjectiveTo determine the overall prognosis for CAE patients.Materials and methodsThis study was a retrospective cohort study. Fifty-one patients with CAE and comorbid AMI (CAE + AMI) and 108 patients with CAE and comorbid CHD (CAE + CHD) were enrolled and matched to non-CAE subjects at a ratio of 1:3 using a propensity score method, respectively. Controls for CAE + AMI group were 153 AMI patients, controls for CAE group were 324 CHD patients and 329 participants with relatively normal coronary arteries (CON). We followed them up to observe major cardiovascular events (MACE).ResultsThe Kaplan-Meier curves showed that the prognosis in CAE + AMI group was worse than in AMI group (5-year non-MACE rate: 62.70% vs. 79.70%, P = 0.010), the prognosis in CAE group was worse than in CHD and CON groups (5-year non-MACE rate: 74.10% vs. 85.80% and 96.70%, respectively, P = 0.000). The main MACEs in CAE + AMI and CAE groups were AMI reoccurrence (19.61% vs. 4.57%, P = 0.002) and re-hospitalization due to repeated angina pectoris (14.81% vs. 8.33% and 2.74%, P = 0.000), respectively. Additionally, the COX regression analysis revealed that the protective factors for preventing MACE in CAE + AMI group included antiplatelet agents (hazard ratio = 0.234, P = 0.016) and angiotensin-converting enzyme inhibitor/angiotensin receptor inhibitor (ACEI/ARB, hazard ratio = 0.317, P = 0.037). Whereas the main factor promoting MACE in CAE group was the degree of coronary stenosis (Gensini score, hazard ratio = 1.011, P = 0.022).ConclusionThe prognosis of patients with CAE + AMI was worse than that of those with AMI. The overall prognosis of patients with CAE was worse than that of those with CHD. CAE + AMI and CAE groups had different characteristics; the former was prone to AMI reoccurrence, and the latter was prone to repeated angina pectoris. To prevent MACE, medications, including antiplatelets and ACEI/ARBs, are indicated for patients with CAE + AMI, whereas prevention of the progression of atherosclerotic lesions is indicated for patients with CAE.

The uncontrollable COVID-19 crises in the SARS-CoV-2 high-prevalence areas have greatly disrupted the routine treatment of liver cancer and triggered a role transformation of radiotherapy for liver cancer. The weight of radiotherapy in the treatment algorithm for liver cancer has been enlarged by the COVID-19 pandemic, which is helpful for the optimal risk-benefit profile.

BackgroundActive surveillance has been considered a safe alternative to surgery for low-risk papillary thyroid microcarcinoma. This study aimed to assess the oncological outcomes and psychological status of active surveillance of highly suspicious thyroid nodules ≤10 mm in China.MethodsThis prospective single-center cohort study enrolled 336 patients with highly suspicious thyroid nodules for active surveillance to assess oncological outcomes and psychological status. The psychological status of patients was assessed by two different questionnaires and compared among different patient groups.ResultsDuring a median follow-up period of 28.5 months, eight patients underwent delayed surgery for tumor enlargement and one for lymph node metastases. The cumulative incidence of disease progression at 5 and 10 years was 6.0% and 12.8%, respectively. Patients who underwent delayed surgery had no permanent complications, and no patient had distant metastasis or death. Patients ≤30 years old had a higher baseline anxiety score (4.9 vs. 3.8, p=0.024), a higher proportion of baseline anxiety score, i.e., ≥8 points (24.0% vs. 12.6%, p=0.033), and a worse baseline emotional function (62.7 vs. 70.7, p=0.013) than patients >30. During AS, patients ≤30 years of age had higher overall anxiety levels (p=0.005) and a worse overall emotional function (p=0.001).ConclusionsActive surveillance in Chinese patients with highly suspicious subcentimetre thyroid nodules has good oncological outcomes and can be used as a safe alternative to surgery. Younger patients (≤30) show a worse psychological status; therefore, more attention should be paid to younger patients.

In order to study the dynamic stress distribution and the fracture area of rock around the tunnel under different orientations of blasting disturbance, AUTODYN finite difference method software was used to conduct numerical simulation research. Gauge monitoring points were set around the numerical model of the tunnel to conduct real-time monitoring of the stress distribution, displacement and fracture area of the tunnel. Based on the analysis of the stress wave propagation law, the following conclusions are obtained: (1) under the condition of the same blasting loads, the stress and displacement of the tunnel is relatively small when the blasting disturbance source is located above the roof, i.e., the stress state of the tunnel is relatively stable and the fracture area around the tunnel is minimal; (2) from the uniaxial stress around the tunnel and the tunnel peripheral displacement, it can be seen that the displacement caused by horizontal direction stress of the tunnel is the largest, and the deformation is mainly concentrated above the floor and at the shoulder, while the vertical wall part has almost no deformation; (3) for brittle materials such as rock, the arch-shaped stress-bearing surface is more likely to disperse stress, while the straight wall and flat floor of the tunnel cannot well disperse stress, resulting in uneven stress on the stress-bearing surface, uncoordinated deformation and ultimately, failure.

Abstract Background A combination of programmed cell death protein‐1 (PD‐1)/programmed cell death ligand‐1 (PD‐L1) inhibitors and radiotherapy (RT) is increasingly being used to treat non‐small‐cell lung cancer (NSCLC). However, the safety and efficacy of this approach remains controversial. We performed a systematic review and meta‐analysis to summarize the related research. Methods We searched the China Biology Medicine, EMBASE, Cochrane Library, and PubMed databases for all the relevant studies. The Stata software, version 12.0 was used for the meta‐analysis. Results The study included 20 clinical trials that enrolled 2027 patients with NSCLC. Compared with non‐combination therapy, combination therapy using PD‐1/PD‐L1 inhibitors and RT was associated with prolonged overall survival (OS) (1‐year OS: odds ratio [OR] 1.77, 95% confidence interval [CI] 1.35–2.33, p = 0.000; 2‐year OS: OR 1.77, 95% CI 1.35–2.33, p = 0.000) and progression‐free survival (PFS) (0.5‐year PFS: OR 1.83, 95% CI 1.13–2.98, p = 0.014; 1‐year PFS: OR 2.09, 95% CI 1.29–3.38, p = 0.003; 2‐year PFS: OR 2.47, 95% CI 1.13–5.37, p = 0.023). Combination therapy also improved the objective response rate (OR 2.76, 95% CI 1.06–7.19, p = 0.038) and disease control rate (OR 1.80, 95% CI 1.21–2.68, p = 0.004). This meta‐analysis showed that compared with non‐combination therapy, combination therapy using PD‐1/PD‐L1 inhibitors and RT did not increase the serious adverse event rates (≥grade 3); however, this approach increased the rate of grade 1–2 immune‐related or radiation pneumonitis. Subgroup analyses revealed that the sequence of PD‐1/PD‐L1 inhibitors followed RT outperformed in which concurrent PD‐1/PD‐L1 inhibitor and RT followed PD‐1/PD‐L1 inhibitor. Combination of stereotactic body RT or stereotactic radiosurgery with PD‐1/PD‐L1 inhibitors may be more effective than a combination of conventional RT with PD‐1/PD‐L1 inhibitors in patients with advanced NSCLC. Conclusion Combination therapy using PD‐1/PD‐L1 inhibitors and RT may improve OS, PFS, and tumor response rates without an increase in serious adverse events in patients with advanced NSCLC. However, combination therapy was shown to increase the incidence of mild pneumonitis.

This study uses a discrete choice experiment to examine consumers’ preferences for Fuji apple product attributes and willingness to pay (WTP) estimates for consumers in six cities in China. We estimated the preference heterogeneity by linking the stated preference choice data with consumers’ past experience and socioeconomic characteristics in the latent class model. The empirical results show that, first, the past experience variables are crucial in explaining consumer preferences and WTP. Second, three classes, namely, certification-oriented, price- and origin-oriented, and not interested, are identified. Furthermore, the same type of Fuji apple attribute does not appeal to every respondent. Third, our results indicate the heterogeneity of preferences across different classes of respondents, as well as differences in WTP for Fuji apples.

Abstract Background This study's initial results revealed significant decreases in treatment‐related esophagitis and pneumonitis cases in patients with thoracic esophageal squamous cell carcinoma (ESCC) treated with involved‐field irradiation (IFI), compared to elective nodal irradiation (ENI). This report outlines the long‐term trial results, specifically; overall survival (OS), progression‐free survival (PFS), metastasis‐free survival (MFS), and locoregional progression‐free survival (LRFS). Materials and Methods Stage II–III thoracic ESCC patients were assigned randomly, in a 1:1 ratio, into either the ENI or IFI arm. Radiation therapy was delivered once a day in 1.8‐2.0 Gy fractions to a total dose of 60.0‐66.0 Gy to the gross tumor volume and 50.0‐54.0 Gy to the clinical target volume. The primary endpoints were acute treatment‐related esophagitis and pneumonitis. The results for the primary endpoints were previously published in 2018. In this article, we analyzed the secondary endpoints including PFS, LRFS, MFS, and OS. Results Between April 2012 and October 2016, 228 patients from nine participating centers in China were enrolled into this study and randomly assigned to two treatment groups. For ENI and IFI groups, respectively, the results showed similarity and were as follows: median PFS (20.3 months vs 21.4 months), OS (32.5 months vs 34.9 months), MFS (28.2 months vs 26.0 months), and LRFS (25.0 months vs 26.6 months). In particular, respective OS rates in the ENI and IFI groups were 84.6% and 82.5% after 1 year, 45.1% and 48.7% after 3 years, and 29.8% and 30.7% at 5 years. PFS rates after 1, 3, and 5 years were 58.9%, 34.2%, and 26.9%, respectively, in the ENI arm compared to 64.4%, 30.8%, and 27.7%, respectively, in the IFI arm. Multivariate analysis identified clinical stage and tumor responses as independent predictors of OS. Meanwhile, tumor location, cStage, and tumor response were identified as independent factors influencing PFS. Conclusion IFI was associated with similar survival as ENI in patients with thoracic ESCC, suggesting that IFI is an acceptable treatment method for thoracic ESCC.

Abstract Malignant melanomas (MMs) were the fifth most common cancer in men and the sixth most common cancer in women in 2018, respectively. These are characterized by high metastatic rates and poor prognoses. We systematically reviewed safety and efficacy of carbon‐ion radiotherapy (CIRT) for treating MMs. Eleven studies were eligible for review, and the data showed that MM patients showed better local control with low recurrence and mild toxicities after CIRT. Survival rates were slightly higher in patients with cutaneous or uveal MMs than in those with mucosal MMs. CIRT in combination with chemotherapy produced higher progression‐free survival rates than CIRT only. In younger patients, higher rates of distant metastases of gynecological MMs were observed. The data indicated that CIRT is effective and safe for treating MMs; however, a combination with systemic therapy is recommended to ensure the best possible prognosis for MMs.

Abstract Background This study investigated neutrophil activation and neutrophil-derived extracellular traps formation in coronary artery ectasia. Methods We enrolled 90 patients who underwent coronary angiography, and included 30 patients with coronary artery ectasia (CAE), 30 patients with obstructive coronary artery disease (CAD) and 30 patients with normal coronary arteries (CON). Intra-neutrophil mean myeloperoxidase index (MPXI) was determined using an automated blood cell counter (ADVIA2120 Hematology System). Serum concentrations of plasma adhesion molecules, cytokines, and neutrophil-derived extracellular traps were quantified. Results The intra-neutrophil mean myeloperoxidase index was reduced in CAE patients compared to CAD and CON patients (1.02 ± 3.01, 3.22 ± 3.03, 3.52 ± 4.25, respectively; CAE vs CAD, p = 0.016 and CAE vs CON, p = 0.007). Multiple logistic regression analysis showed that MPXI and dsDNA were independent factors that predicted the presence of CAE. CAE patients had higher levels of plasma adhesion molecules (P-selectin glycoprotein ligand-1, E-selectin, L-selectin) and interleukin 1 beta levels. Neutrophil extracellular trap concentrations were significantly higher in the CAE group compared to CAD and CON patients (284.31(258.33–449.91) ng/mL, 225.12(203.34–257.13) ng/mL, and 247.37(231.04–273.01) ng/mL, respectively; CAE vs CAD, p = 0.000 and CAE vs CON, p = 0.001). Conclusions Peripheral neutrophils from CAE patients were activated and neutrophil extracellular traps were elevated in the plasma. IL-1β and soluble adhesion molecules may be the causal factors for neutrophil activation.

We aimed to evaluate the relevance of large-volume lateral lymph node metastases (LLNMs) at risk of recurrence/persistence in papillary thyroid carcinoma (PTC) with LLNMs (N1b). This retrospective study included 448 PTC patients, who had positive LLNMs confirmed by histology and suspected of LLNMs by preoperative ultrasound. According to the number of pathological LLNMs, patients were divided into large-volume LLNM (number of LLNMs >5) and low-volume LLNM (number of LLNMs ≤5). Risk factors of recurrence/persistence in PTC patients with N1b were analyzed. Preoperative ultrasound features of PTC with large-volume LLNM were analyzed. For the patients with a mean follow-up of 44.0 months, the risk of recurrence/persistence was 25.1% in PTC patients with N1b. The recurrence/persistence rate was significantly higher in patients with large-volume LLNM than in patients with low-volume LLNM by multivariate analysis (37.3% vs. 17.1%; HR = 2.451, 95% CI 1.41–4.261, p = 0.001). The 3-year and 5-year recurrence/persistence-free survival for those with large-volume LLNM were 93.2% and 47.2%, respectively. Moreover, we found that multilevel suspected LLNMs and loss of fatty hilum were independent preoperative indicative factors of large-volume LLNM (OR = 6.239, 95% CI 3.547–10.977, p < 0.001; OR = 5.149, 95% CI 1.859–14.261, p = 0.002). In conclusion, multilevel suspected LLNM and loss of fatty hilum on ultrasound tended to be more common in patients with large-volume LLNM. PTC patients with large-volume LLNM are at a higher recurrent/persistent risk than those with low-volume LLNM. Large-volume LLNM may be used to stratify the risk of recurrence/persistence in PTC.

PurposeGiven the higher precision accompanied by optimized sparing of normal tissue, charged particle therapy was thought of as a promising treatment for pancreatic cancer. However, systematic preclinical studies were scarce. We aimed to investigate the radiobiological effects of charged particle irradiation on pancreatic cancer cell lines.MethodsA systematic literature search was performed in EMBASE (OVID), Medline (OVID), and Web of Science databases. Included studies were in vitro English publications that reported the radiobiological effects of charged particle irradiation on pancreatic cancer cells.ResultsThirteen carbon ion irradiation and seven proton irradiation in vitro studies were included finally. Relative biological effectiveness (RBE) values of carbon ion irradiation and proton irradiation in different human pancreatic cancer cell lines ranged from 1.29 to 4.5, and 0.6 to 2.1, respectively. The mean of the surviving fraction of 2 Gy (SF2) of carbon ion, proton, and photon irradiation was 0.18 ± 0.11, 0.48 ± 0.11, and 0.57 ± 0.13, respectively. Carbon ion irradiation induced more G2/M arrest and a longer-lasting expression of γH2AX than photon irradiation. Combination therapies enhanced the therapeutic effects of pancreatic cell lines with a mean standard enhancement ratio (SER) of 1.66 ± 0.63 for carbon ion irradiation, 1.55 ± 0.27 for proton irradiation, and 1.52 ± 0.30 for photon irradiation. Carbon ion irradiation was more effective in suppressing the migration and invasion than photon irradiation, except for the PANC-1 cells.ConclusionsCurrent in vitro evidence demonstrates that, compared with photon irradiation, carbon ion irradiation offers superior radiobiological effects in the treatment of pancreatic cancer. Mechanistically, high-LET irradiation may induce complex DNA damage and ultimately promote genomic instability and cell death. Both carbon ion irradiation and proton irradiation confer similar sensitization effects in comparison with photon irradiation when combined with chemotherapy or targeted therapy.

Information attributes characterize traceable agri-food. The perceived value of information attributes influences consumers’ preferences for traceable agri-food, consisting of two dimensions, predictive value and confidence value. We examine heterogeneous preferences and willingness to pay (WTP) in China’s traceable agri-food market. Using the choice experiments, we explore how the traceability information, certification type, region of origin, and price influence Chinese consumers’ Fuji apple choices. We identify three consumer classes by a latent class model: certification-oriented class (65.8%), price-sensitive and origin-oriented class (15.0%), and no-buy class (19.2%). The results show that consumer sociodemographic characteristics, predictive value, and confidence value are the heterogeneous sources that determine their preferences for Fuji apple information attributes. Specifically, consumers’ age, family income per month, and whether the family has children under 18 significantly impact the membership probability of consumers in both certification-oriented and price-sensitive and origin-oriented classes. Consumers’ predicted value and confidence value significantly impact the membership probability of consumers in the certification-oriented class. In contrast, consumers’ predicted value and confidence value have no significant impact on the membership probability of consumers in price-sensitive and origin-oriented class.