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Immune checkpoint blockade targeting the CD47/SIRPα axis represents an alluring avenue for cancer immunotherapy. However, the compromised efficacy and safety concerns in vivo of conventional anti-CD47 antibodies impede their wide clinical applications. Here we introduced a single type of high-mannose glycans into the nanobodies against CD47 (HM-nCD47) and subsequently displayed HM-nCD47 on cellular vesicles (CVs) for enhanced cancer immunotherapy. In this platform, the CVs significantly improved the circulation time of HM-nCD47-CVs, the nCD47 enabled the blockade of the CD47/SIRPα axis, and the HM enhanced recognition of mannose-binding lectin, all synergistically activating the macrophage-mediated antitumor immunity. In both subcutaneous and metastatic murine tumor models, the HM-nCD47-CVs possessed significantly extended half-lives and increased accumulation at the tumor site, resulting in a remarkable macrophage-dependent inhibition of tumor growth, a transcriptomic remodeling of the immune response, and an increase in survival time. By integrating the chemical biology toolbox with cell membrane nanotechnology, the HM-nCD47-CVs represent a new immunotherapeutic platform for cancer and other diseases.
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Background: Macrophages play a crucial role in the progression of AF, closely linked to atrial inflammation and myocardial fibrosis. However, the functions and molecular mechanisms of different phenotypic macrophages in AF are not well understood. This study aims to analyze the infiltration characteristics of atrial immune cells in AF patients and further explore the role and molecular expression patterns of M2 macrophage-related genes in AF. Methods: This study integrates single-cell and large-scale sequencing data to analyze immune cell infiltration and molecular characterization of the LAA in patients with AF, using SR as a control group. CIBERSORT assesses immune cell types in LAA tissues; WGCNA identifies signature genes; cell clustering analyzes cell types and subpopulations; cell communication explores macrophage interactions; hdWGCNA identifies M2 macrophage gene modules in AF. AF biomarkers are identified using LASSO and Random Forest, validated with ROC curves and RT-qPCR. Potential molecular mechanisms are inferred through TF-miRNA-mRNA networks and single-gene enrichment analyses. Results: Myeloid cell subsets varied considerably between the AF and SR groups, with a significant increase in M2 macrophages in the AF group. Signals of inflammation and matrix remodeling were observed in AF. M2 macrophage-related genes IGF1, PDK4, RAB13, and TMEM176B were identified as AF biomarkers, with RAB13 and TMEM176B being novel markers. A TF-miRNA-mRNA network was constructed using target genes, which are enriched in the PPAR signaling pathway and fatty acid metabolism. Conclusion: Over infiltration of M2 macrophages may be an important factor in the progression of AF. The M2 macrophage-related genes IGF1, RAB13, TMEM176B and PDK4 may regulate the progression of AF through the PPAR signaling pathway and fatty acid metabolism.
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OBJECTIVES: Ultrasound imaging (USI) is the gold standard in the clinical diagnosis of thyroid diseases. Compared with two-dimensional (2D) USI, three-dimensional (3D) USI could provide more structural information. However, the unstable pressure generated by the hand-hold ultrasound probe scanning can cause tissue deformation, especially in soft tissues such as the thyroid. The deformation is manifested as tissue structure being compressed in 2D USI, which results in structural discontinuity in 3D USI. Furthermore, multiple scans apply pressure in different directions to the tissue, which will cause relative displacement between the 3D images obtained from multiple thyroid scans. METHODS: In this work, we proposed a framework to minimize the influence of the variation of pressure in thyroid 3D USI. To correct pressure artifacts in a single scanning sequence, an adaptive method to smooth the position of the 2D ultrasound (US) image sequence is adopted before performing volumetric reconstruction. To build a whole 3D US image including both sides of the thyroid gland, an iterative closest point (ICP) based registration pipeline is adopted to eliminate the relative displacement caused by different pressure directions. RESULTS: Our proposed method was validated by in vivo experiments, including healthy volunteers and volunteers with thyroid nodules at different grading levels. CONCLUSIONS: The thyroid gland and nodule are rendered intelligently in the whole scanning region to facilitate the observation of 3D USI results by the doctor. This work might make a positive contribution to the clinical diagnosis of diseases of the thyroid or other soft tissues.
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Imageamento Tridimensional , Doenças da Glândula Tireoide , Glândula Tireoide , Ultrassonografia , Humanos , Ultrassonografia/métodos , Glândula Tireoide/diagnóstico por imagem , Imageamento Tridimensional/métodos , Doenças da Glândula Tireoide/diagnóstico por imagem , Feminino , Adulto , Masculino , Nódulo da Glândula Tireoide/diagnóstico por imagemRESUMO
Background and Purpose: Artificial intelligence (AI) is a technique which tries to think like humans and mimic human behaviors. It has been considered as an alternative in a lot of human-dependent steps in radiotherapy (RT), since the human participation is a principal uncertainty source in RT. The aim of this work is to provide a systematic summary of the current literature on AI application for RT, and to clarify its role for RT practice in terms of clinical views. Materials and Methods: A systematic literature search of PubMed and Google Scholar was performed to identify original articles involving the AI applications in RT from the inception to 2022. Studies were included if they reported original data and explored the clinical applications of AI in RT. Results: The selected studies were categorized into three aspects of RT: organ and lesion segmentation, treatment planning and quality assurance. For each aspect, this review discussed how these AI tools could be involved in the RT protocol. Conclusions: Our study revealed that AI was a potential alternative for the human-dependent steps in the complex process of RT.
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Glycans, with their variable compositions and highly dynamic conformations, vastly expand the heterogeneity of whatever factor or cell they are attached to. These properties make them crucial contributors to biological function and organismal health and also very difficult to study. That may be changing as we look to the future of glycobiology.
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Glicômica , Polissacarídeos , Animais , Humanos , Polissacarídeos/metabolismo , Polissacarídeos/químicaRESUMO
This article proposes an improved A* algorithm aimed at improving the logistics path quality of automated guided vehicles (AGVs) in digital production workshops, solving the problems of excessive path turns and long transportation time. The traditional A* algorithm is improved internally and externally. In the internal improvement process, we propose an improved node search method within the A* algorithm to avoid generating invalid paths; offer a heuristic function which uses diagonal distance instead of traditional heuristic functions to reduce the number of turns in the path; and add turning weights in the A* algorithm formula, further reducing the number of turns in the path and reducing the number of node searches. In the process of external improvement, the output path of the internally improved A* algorithm is further optimized externally by the improved forward search optimization algorithm and the Bessel curve method, which reduces path length and turns and creates a path with fewer turns and a shorter distance. The experimental results demonstrate that the internally modified A* algorithm suggested in this research performs better when compared to six conventional path planning methods. Based on the internally improved A* algorithm path, the full improved A* algorithm reduces the turning angle by approximately 69% and shortens the path by approximately 10%; based on the simulation results, the improved A* algorithm in this paper can reduce the running time of AGV and improve the logistics efficiency in the workshop. Specifically, the walking time of AGV on the improved A* algorithm path is reduced by 12s compared to the traditional A* algorithm.
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E0703, a new steroidal compound optimized from estradiol, significantly increased cell proliferation and the survival rate of KM mice and beagles after ionizing radiation. In this study, we characterize its preclinical pharmacokinetics (PK) and predict its human PK using a physiologically based pharmacokinetic (PBPK) model. The preclinical PK of E0703 was studied in mice and Rhesus monkeys. Asian human clearance (CL) values for E0703 were predicted from various allometric methods. The human PK profiles of E0703 (30 mg) were predicted by the PBPK model in Gastro Plus software 9.8 (SimulationsPlus, Lancaster, CA, USA). Furthermore, tissue distribution and the human PK profiles of different administration dosages and forms were predicted. The 0.002 L/h of CL and 0.005 L of Vss in mice were calculated and optimized from observed PK data. The plasma exposure of E0703 was availably predicted by the CL using the simple allometry (SA) method. The plasma concentration-time profiles of other dosages (20 and 40 mg) and two oral administrations (30 mg) were well-fitted to the observed values. In addition, the PK profile of target organs for E0703 exhibited a higher peak concentration (Cmax) and AUC than plasma. The developed E0703-PBPK model, which is precisely applicable to multiple species, benefits from further clinical development to predict PK in humans.
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Protetores contra Radiação , Camundongos , Humanos , Animais , Cães , Modelos Biológicos , Administração Oral , Distribuição Tecidual , FarmacocinéticaRESUMO
Accurate delineation of the clinical target volume (CTV) is a crucial prerequisite for safe and effective radiotherapy characterized. This study addresses the integration of magnetic resonance (MR) images to aid in target delineation on computed tomography (CT) images. However, obtaining MR images directly can be challenging. Therefore, we employ AI-based image generation techniques to "intelligentially generate" MR images from CT images to improve CTV delineation based on CT images. To generate high-quality MR images, we propose an attention-guided single-loop image generation model. The model can yield higher-quality images by introducing an attention mechanism in feature extraction and enhancing the loss function. Based on the generated MR images, we propose a CTV segmentation model fusing multi-scale features through image fusion and a hollow space pyramid module to enhance segmentation accuracy. The image generation model used in this study improves the peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM) from 14.87 and 0.58 to 16.72 and 0.67, respectively, and improves the feature distribution distance and learning-perception image similarity from 180.86 and 0.28 to 110.98 and 0.22, achieving higher quality image generation. The proposed segmentation method demonstrates high accuracy, compared with the FCN method, the intersection over union ratio and the Dice coefficient are improved from 0.8360 and 0.8998 to 0.9043 and 0.9473, respectively. Hausdorff distance and mean surface distance decreased from 5.5573 mm and 2.3269 mm to 4.7204 mm and 0.9397 mm, respectively, achieving clinically acceptable segmentation accuracy. Our method might reduce physicians' manual workload and accelerate the diagnosis and treatment process while decreasing inter-observer variability in identifying anatomical structures.
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Plitidepsin (or dehydrodidemnin B), an approved anticancer drug, belongs to the didemnin family of cyclic depsipeptides, which are found in limited quantities in marine tunicate extracts. Herein, we introduce a new approach that integrates microbial and chemical synthesis to generate plitidepsin and its analogues. We screened a Tistrella strain library to identify a potent didemnin B producer, and then introduced a second copy of the didemnin biosynthetic gene cluster into its genome, resulting in a didemnin B titer of approximately 75â mg/L. Next, we developed two straightforward chemical strategies to convert didemnin B into plitidepsin, one of which involved a one-step synthetic route giving over 90 % overall yield. Furthermore, we synthesized 13 new didemnin derivatives and three didemnin probes, enabling research into structure-activity relationships and interactions between didemnin and proteins. Our study highlights the synergistic potential of biosynthesis and chemical synthesis in overcoming the challenge of producing complex natural products sustainably and at scale.
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Antineoplásicos , Depsipeptídeos , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/metabolismo , Depsipeptídeos/farmacologia , Antineoplásicos/farmacologia , Relação Estrutura-AtividadeRESUMO
Purpose: The purpose of this study is to develop a freehand scan three-dimensional (3D) shear wave elasticity imaging (SWEI) method for characterizing the anisotropy of elastic properties in biological tissues. The motivation behind this work lies in addressing the limitations of traditional two-dimensional (2D) SWEI, which only measures shear wave speeds in a single direction, as well as fulfilling the clinical demand for improved medical imaging. Approach: Our imaging system utilizes a high-definition optical camera to continuously track the ultrasonic transducer, collecting spatial position-angle data of the transducer and corresponding two-dimensional SWEI data. By reconstructing three-dimensional SWEI images using these data, we achieved freehand SWEI. Results: We validated the accuracy of 2D SWEI on a standard elastic phantom, and then performed 3D SWEI on the pork tenderloin and the triceps brachii of two volunteers. We obtained shear wave speed of 1.82 to 3.12 m/s in the pork tenderloin, shear wave speed of 1.16 to 2.36 m/s in the triceps brachii of non-exercising volunteers, and shear wave speed of 0.55 to 1.63 m/s in the triceps brachii of exercising volunteers, and the maximum shear wave speed directions were generally aligned with the orientation of muscle fibers. Conclusions: We proposed a method that can overcome the limitations of 2D-SWEI regarding imaging angle while also extending the imaging angle of 3D-SWEI, which could have significant implications for improving the accuracy and safety of medical diagnoses.
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OBJECTIVES: To observe the effects of electroacupuncture(EA) on memory, cognitive impairment, and the brain-derived neurotrophic factor(BDNF)/N-methyl-D-aspartate receptor subtype 1(NMDAR1) pathway in the brains of offspring rat with intrauterine growth restriction(IUGR) induced by perinatal nicotine exposure(PNE), so as to explore the underlying mechanism. METHODS: SD rats were randomly divided into normal, model, and EA groups, with 4 mothers and 10 offspring rats of each mother in each group. The IUGR model was established by subcutaneous injection of nicotine during pregnancy and lactation. From the 6th day of pregnancy in the mothers until the 21st day after birth of the offspring rats, EA (2 Hz/15 Hz, 1 mA) was administered bilaterally at the "Zusanli"(ST36) of mothers, once daily for 20 min. The brain organ coefficient was used to evaluate the brain development of the offspring rats. The Y-maze test and novel object recognition experiments were performed to assess memory and cognitive function. HE staining was used to observe the development and cellular morphology of the hippocampus and prefrontal cortex in the offspring rats. UV spectrophotometry was used to measure the glutamate(Glu) content in the hippocampus. ELISA was used to detect the BDNF content in the hippocampus. Western blot was performed to measure the protein expression of NMDAR1 in the hippocampus. Immunohistochemistry was used to count the number of BDNF-positive cells in the hippocampus and prefrontal cortex. RESULTS: Compared with the normal group, the brain organ coefficient, exploration time of the novel arm, spontaneous alternation rate, and novel object recognition index, contents of BDNF and expression of NMDAR1 proteins in the hippocampus, the number of BDNF-positive cells in the CA1 and CA3 regions of the hippocampus and prefrontal cortex were significantly reduced(P<0.01), while the Glu content in the hippocampus was significantly increased(P<0.01) in the model group of offspring ratsï¼decreased cell number, scattered arrangement, and disrupted cellular structure were observed in the hippocampus and prefrontal cortex of offspring rats in the model group. Compared with the model group, the brain organ coefficient, exploration time of the novel arm, spontaneous alternation rate, and novel object recognition index, the BDNF contents and NMDAR1 protein expression in the hippocampus, the number of BDNF-positive cells in the hippocampal CA1 and CA3 regions and prefrontal cortex significantly increased(P<0.01, P<0.05), while the Glu content in the hippocampus was significantly decreased (P<0.01) in offspring rats of the EA groupï¼increased cell number, neat arrangement, and reduced cellular damage were observed in the hippocampus and prefrontal cortex in the EA group. CONCLUSIONS: EA has an improving effect on memory and cognitive function impairment in offspring rats with IUGR induced by PNE, and this mechanism may be associated with the regulation of BDNF/NMDAR1 pathway, thereby improving the neuronal quantity and structure of the hippocampus and prefrontal cortex in offspring rats.
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Disfunção Cognitiva , Eletroacupuntura , Gravidez , Feminino , Ratos , Animais , Ratos Sprague-Dawley , Nicotina/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Disfunção Cognitiva/genética , Disfunção Cognitiva/terapia , Ácido Glutâmico/metabolismoRESUMO
Efficient clearance of dying cells (efferocytosis) is an evolutionarily conserved process for tissue homeostasis. Genetic enhancement of efferocytosis exhibits therapeutic potential for inflammation resolution and tissue repair. However, pharmacological approaches to enhance efferocytosis remain sparse due to a lack of targets for modulation. Here, we report the identification of columbamine (COL) which enhances macrophage-mediated efferocytosis and attenuates intestinal inflammation in a murine colitis model. COL enhances efferocytosis by promoting LC3-associated phagocytosis (LAP), a non-canonical form of autophagy. Transcriptome analysis and pharmacological characterization revealed that COL is a biased agonist that occupies a part of the ligand binding pocket of formyl peptide receptor 2 (FPR2), a G-protein coupled receptor involved in inflammation regulation. Genetic ablation of the Fpr2 gene or treatment with an FPR2 antagonist abolishes COL-induced efferocytosis, anti-colitis activity and LAP. Taken together, our study identifies FPR2 as a potential target for modulating LC3-associated efferocytosis to alleviate intestinal inflammation and highlights the therapeutic value of COL, a natural and biased agonist of FPR2, in the treatment of inflammatory bowel disease.
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Colite , Camundongos , Animais , Fagocitose , Transdução de Sinais , Inflamação/genética , Macrófagos/metabolismo , Colite/metabolismoRESUMO
N6-methyladenosine (m6A) is the most abundant internal mRNA nucleotide modification in mammals, regulating critical aspects of cell physiology and differentiation. The YTHDF proteins are the primary readers of m6A modifications and exert physiological functions of m6A in the cytosol. Elucidating the regulatory mechanisms of YTHDF proteins is critical to understanding m6A biology. Here we report a mechanism that protein post-translational modifications control the biological functions of the YTHDF proteins. We find that YTHDF1 and YTHDF3, but not YTHDF2, carry high levels of nutrient-sensing O-GlcNAc modifications. O-GlcNAcylation attenuates the translation-promoting function of YTHDF1 and YTHDF3 by blocking their interactions with proteins associated with mRNA translation. We further demonstrate that O-GlcNAc modifications on YTHDF1 and YTHDF3 regulate the assembly, stability and disassembly of stress granules to enable better recovery from stress. Therefore, our results discover an important regulatory pathway of YTHDF functions, adding an additional layer of complexity to the post-transcriptional regulation function of mRNA m6A.
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Processamento de Proteína Pós-Traducional , Proteínas , Animais , Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação da Expressão Gênica , Mamíferos/metabolismoRESUMO
Hepatitis E virus (HEV) is a significant public health concern worldwide. Pregnant women are at high risk of severe HEV infection. Various adverse outcomes in pregnant women related to HEV infection have been well documented in low-income and middle-income countries with poor sanitation. However, previous studies have provided inconsistent conclusions regarding the effects of HEV infection on the health of pregnant women and their infants in developed countries and contemporary China. In China, previous studies on HEV in pregnant women mainly focused on anti-HEV IgM and/or anti-HEV IgG. In this study, 4244 pregnant women were retrospectively analyzed for HEV-related markers. The positive rates of HEV antigen, HEV RNA, anti-HEV IgM, and anti-HEV IgG were 0.28%, 0.54%, 0.35%, and 10.49%, respectively. Among the 467 pregnant women who tested positive for at least one HEV-related marker, 92.93% (434) were positive for anti-HEV IgG only and 0.21% (1) were positive for HEV antigen, anti-HEV IgM, and anti-HEV IgG. Although the prevalence of anti-HEV IgG significantly increased with age, the prevalence of anti-HEV IgM, HEV RNA, and HEV antigen did not differ among pregnant women of different ages. Thirty-three pregnant women were positive for at least one of anti-HEV IgM, HEV antigen, and HEV RNA, and these individuals were recently or currently infected with HEV. None of the 33 pregnant women exhibited obvious clinical symptoms. Of the 33 pregnant women, 39.39% (13) experienced adverse fetal outcomes, including preterm birth, fetal distress, and low birth weight, the incidence of which was significantly higher than in pregnant women who were not recently or currently infected with HEV. These findings suggest that maternal HEV infection may impact the health of fetuses; thus, these results may contribute to the development of appropriate public health interventions for this population.
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BACKGROUND: The pathophysiological characteristics of the respiratory system of obese patients differ from those of non-obese patients. Few studies have evaluated the effects of high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV) on the prognosis of obese patients. We here compared the effects of these two techniques on the prevention of reintubation after extubation for obese patients. METHODS: Data were extracted from the Medical Information Mart for Intensive Care database. Patients who underwent HFNC or NIV treatment after extubation were assigned to the HFNC or NIV group, respectively. The reintubation risk within 96 hours postextubation was compared between the two groups using a doubly robust estimation method. Propensity score matching was performed for both groups. RESULTS: This study included 757 patients (HFNC group: n=282; NIV group: n=475). There was no significant difference in the risk of reintubation within 96 hours after extubation for the HFNC group compared with the NIV group (OR 1.50, p=0.127). Among patients with body mass index ≥40 kg/m2, the HFNC group had a significantly lower risk of reintubation within 96 hours after extubation (OR 0.06, p=0.016). No significant differences were found in reintubation rates within 48 hours (15.6% vs 11.0%, p=0.314) and 72 hours (16.9% vs 13.0%, p=0.424), as well as in hospital mortality (3.2% vs 5.2%, p=0.571) and intensive care unit (ICU) mortality (1.3% vs 5.2%, p=0.108) between the two groups. However, the HFNC group had significantly longer hospital stays (14 days vs 9 days, p=0.005) and ICU (7 days vs 5 days, p=0.001) stays. CONCLUSIONS: This study suggests that HFNC therapy is not inferior to NIV in preventing reintubation in obese patients and appears to be advantageous in severely obese patients. However, HFNC is associated with significantly longer hospital stays and ICU stays.
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Ventilação não Invasiva , Insuficiência Respiratória , Humanos , Estudos Retrospectivos , Extubação/efeitos adversos , Cânula , Oxigenoterapia/métodos , Insuficiência Respiratória/terapia , Insuficiência Respiratória/prevenção & controle , Obesidade/complicações , Obesidade/terapiaRESUMO
Ultrasound imaging (USI) is a widely adopted imaging method in clinical diagnosis owing to its low cost, convenience, and safety. However, due to the complex acoustic attenuation, two-dimensional (2D) USI lacks the capability to achieve a clear imaging result when the target is shaded by high echo tissues. This paper proposes a three-dimensional (3D) free-scan real-time ultrasound imaging (FRUSI) method. By integrating 2D ultrasound image sequences around the region of interest (ROI) with a real-time and spatially accurate probe tracking method, the proposed FRUSI system provides clear and accurate ultrasound images for medical study. The experiment results on reconstruction precision and accuracy show the potential ability of our proposed system to provide high-quality 3D ultrasound imaging. Moreover, previously shaded targets can be discerned clearly in the same scan plane in both phantom studies and in vivo studies on the human finger joint. The performance of the proposed FRUSI system has demonstrated its potential value for clinical diagnosis to provide high ultrasound imaging quality and rich details in spatial information. Due to the convenient setup, the FRUSI system might potentially be expanded to other ultrasound imaging modalities.
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Artefatos , Imageamento Tridimensional , Humanos , Ultrassonografia , Imageamento Tridimensional/métodos , Imagens de FantasmasRESUMO
Highaltitude acute hypoxia is commonly associated with respiratory cardiovascular diseases. The inability to adapt to acute hypoxia may lead to cardiovascular dysfunction, lung injury and even death. Therefore, understanding the molecular basis of the adaptation to highaltitude acute hypoxia may reveal novel therapeutic approaches with which to counteract the detrimental consequences of hypoxia. In the present study, a highaltitude environment was simulated in a rat model in order to investigate the role of the high mobility group protein1 (HMGB1)/receptor for advanced glycation end products (RAGE)/NFκB and F2/Rho signaling pathways in lung injury induced by acute hypoxia. It was found that acute hypoxia caused inflammation through the HMGB1/RAGE/NFκB pathway and coagulation dysfunction through the F2/Rho pathway, both of which may be key processes in acute hypoxiainduced lung injury. The present study provides new insight into the molecular basis of lung injury induced by acute hypoxia. The simultaneous activation of the HMGB1/RAGE/NFκB and F2/Rho signaling pathways plays a critical role in hypoxiainduced inflammatory responses and coagulation abnormalities, and provides a theoretical basis for the development of potential therapeutic strategies.
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Lesão Pulmonar Aguda , Transtornos da Coagulação Sanguínea , Proteína HMGB1 , Animais , Ratos , NF-kappa B , Receptor para Produtos Finais de Glicação Avançada , Hipóxia/complicações , Lesão Pulmonar Aguda/etiologia , InflamaçãoRESUMO
Background: Cone-beam computed tomography (CBCT) is an important tool for patient positioning in radiotherapy due to its outstanding advantages. However, the CBCT registration shows errors due to the limitations of the automatic registration algorithm and the nonuniqueness of manual verification results. The purpose of this study was to verify the feasibility of using the Sphere-Mask Optical Positioning System (S-M_OPS) to improve the registration stability of CBCT through clinical trials. Methods: From November 2021 to February 2022, 28 patients who received intensity-modulated radiotherapy and site verification with CBCT were included in this study. S-M_OPS was used as an independent third-party system to supervise the CBCT registration result in real time. The supervision error was calculated based on the CBCT registration result and using the S-M_OPS registration result as the standard. For the head and neck, patients with a supervision error ≥3 or ≤-3 mm in 1 direction were selected. For the thorax, abdomen, pelvis, or other body parts, patients with a supervision error ≥5 or ≤-5 mm in 1 direction were selected. Then, re-registration was performed for all patients (selected and unselected). The registration errors of CBCT and S-M_OPS were calculated based on the re-registration results as the standard. Results: For selected patients with large supervision errors, CBCT registration errors (mean ± standard deviation) in the latitudinal (LAT; left/right), vertical (VRT; superior/inferior), and longitudinal (LNG; anterior/posterior) directions were 0.90±3.20, -1.70±0.98, and 7.30±2.14 mm, respectively. The S-M_OPS registration errors were 0.40±0.14, 0.32±0.66, and 0.24±1.12 mm in the LAT, VRT, and LNG directions, respectively. For all patients, CBCT registration errors in the LAT, VRT, and LNG directions were 0.39±2.69, -0.82±1.47, and 2.39±2.93 mm, respectively. The S-M_OPS registration errors were -0.25±1.33, 0.55±1.27, and 0.36±1.34 mm for all patients in the LAT, VRT, and LNG directions, respectively. Conclusions: This study shows that S-M_OPS registration offers comparable accuracy to CBCT for daily registration. S-M_OPS, as an independent third-party tool, can prevent large errors in CBCT registration, thereby improving the accuracy and stability of CBCT registration.
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INTRODUCTION: A combination of zidovudine (AZT), lamivudine (3TC) and lopinavir/ritonavir (LPV/r) is one of the most effective drugs for preventing mother-to-child transmission (PMTCT) of HIV. However, limited information is available regarding its systemic toxicity. This study aimed to investigate its potential toxicity. METHOD: An acute oral toxicity test was conducted to assess the potential acute toxicity of AZT + 3TC + LPV/r. Bacterial reverse mutation, mammalian erythrocyte micronucleus and mouse spermatogonia chromosomal aberration tests were conducted to assess its potential genotoxicity. A 28-day feeding test was conducted to assess the potential subacute toxicity. RESULTS: In mice, the LD50 of the AZT + 3TC + LPV/r mixture was greater than 2000 mg/kg body weight (BW). The rate of micronucleated polychromatic erythrocytes (PCEs) increased in a dose-dependent manner in mice (P < 0.01). After treatment with AZT + 3TC + LPV/r for 28 days, the BW gain of male and female rats in the high-dose group was lower than that in the control group (P < 0.05); the relative weights of the liver, kidney, spleen and brain increased (P < 0.05); and pathological abnormalities appeared in the thyroid and spleen of male and female rats in the high-dose group. The haemoglobin (HGB) and red blood cells (RBCs) count in male and female rats decreased, but the white blood cells (WBCs) and lymphocyte apoptosis rates in male and female rats in the high-dose group increased (P < 0.05). The total protein, albumin, cholesterol and blood glucose levels of male and female rats in the high-dose group were significantly decreased (P < 0.05). The alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) levels of male and female rats in the medium- and high-dose groups increased significantly (P < 0.05). CONCLUSION: The results suggest that AZT + 3TC + LPV/r may exhibit genotoxicity and subacute toxicity under experimental conditions.