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This paper proposes an optimization method aimed at addressing the challenge of balancing system imaging performance and tolerance performance. The method is based on the high-order nodal aberration theory. The calculation method for high-order aberration coefficients is derived, along with the change in aberrations after introducing tolerance perturbation. The evaluation system includes both the imaging performance of the system and its tolerance factors. A comprehensive merit function is created for optimization. Three aspherical system examples were designed for verification, and the optimization results of this method show significantly lower tolerance sensitivity compared to the general optimization results and the SAB function optimization results of CODE V.
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Objective: To evaluate the occurrence, development and outcome value of hyperfluorescent lymphocyte percentage (HFLC%) and immature granulocyte percentage (IG%) for acute pancreatitis (AP). Methods: The laboratory data collected from 1533 patients diagnosed with AP between August 2018 and August 2022 were retrospectively analyzed. The patients were classified into mild acute pancreatitis (MAP) and non-mild acute pancreatitis (Non-MAP) groups; non-MAP groups were additionally subgrouped based on HFLC% at day 7. White blood cells (WBC), HFLC%, and IG% were examined from day 1 (baseline) to day 14 post-admission using Sysmex XN Series Hematology Analyzers. C-reactive protein (CRP), serum amylase (AMY), and lipase (LPS) were detected by Beckman AU5800. Results: A total of 623 patients were finally included in the study [MAP group (n = 358) and Non-MAP group (n = 265)]. WBC, IG%, and CRP were higher in the Non-MAP group from day 1 to day 12 (all P<0.05). The HFLC% was not statistically significant from day 1 to day 6; yet, it increased on day 6 and 7 in the Non-MAP group. We divided patients in the Non-MAP group with complete data(101 patients) into HFLC% ≥ 2.9 %(31 patients) and HFLC% < 2.9 %(70 patients) according to the threshold of 7th day HFLC%. WBC, HFLC%, IG%, and CRP effectively predicted the progression of MAP to Non-MAP (all P < 0.001). HFLC% was the most obvious value, followed by CRP and IG%. Combined with HFLC%, IG%,CRP and WBC in day7, the ROC analysis showed that the area under ROC curve of the combined indicators was the largest (AUC = 0.912, P < 0.001) and had higher sensitivity and specificity than single-item assessment of AP outcomes(P < 0.05). HFLC% < 2.9 %, IG% > 1.7 %, CRP >28.66 mg/L, and WBC >9.24 × 109/L indicated the possibility of AP disease aggravation. Also, HFLC% <2.9 % was directly associated with infection, SIRS, APPACHII grade, and ICU admission (all P < 0.05). In non-MAP there was a significant negative correlation between HFLC% and APACHE-II score (rs = -0.312, P = 0.023). Conclusion: HFLC% <2.9 % on 7th day was directly indicated more infection, systemic inflammatory response syndrome(SIRS), higher APPACH II grade and ICU admission. HFLC% may be an independent laboratory marker for prognosis in AP. Combining HFLC% with IG%, CRP, and WBC helps evaluate AP patients' disease development and outcome.
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Fracture of the alveolar bone resorption is a common complication in orthodontic treatment, which mainly caused by extreme mechanical loading. However, the ferroptosis with orthodontic tooth movement(OTM) relationship has not been thoroughly described. We here analysed whether ferroptosis is involved in OTM-associated alveolar bone loss. Mouse osteoblasts (MC-3T3) and knockdown glutathione peroxidase 4 (GPX4) MC-3T3 were stimulated with compressive force loading and ferrostatin-1 (Fer-1, a ferroptosis inhibitor), and the changes in lipid peroxidation morphology, expression of ferroptosis-related factors and osteogenesis levels were detected. After establishing the rat experimental OTM model, the changes in ferroptosis-related factors and osteogenesis levels were reevaluated in the same manner. Ferroptosis was involved in mechanical stress regulating osteoblast remodelling, and Fer-1 and erastin affected osteoblasts under compression force loading. Fer-1 regulated ferroptosis and autophagy in MC-3T3 and promoted bone proliferation. GPX4-dependent ferroptosis stimulated the YAP (homologous oncoproteins Yes-associated protein) pathway, and GPX4 promoted ferroptosis via the YAP-TEAD (transcriptional enhanced associate domain) signal pathway under mechanical compression force. The in vivo experiment results were consistent with the in vitro experiment results. Ferroptosis transpires during the motion of orthodontic teeth, with compression force side occurring earlier than stretch side within 4 h. GPX4 plays an important role in alveolar bone loss, while Fer-1 can inhibit the compression force-side alveolar bone loss. GPX4's Hippo-YAP pathway is activated by the lack of compression force in the lateral alveolar bone.
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Perda do Osso Alveolar , Ferroptose , Camundongos , Ratos , Animais , Osteogênese/fisiologia , Estresse Mecânico , Transdução de SinaisRESUMO
BACKGROUND: Erectile dysfunction (ED), defined as the inability to achieve or maintain a penile erection sufficient to satisfy sexual behavior, is prevalent worldwide. AIM: Using previous research, bioinformatics, and experimental confirmation, we aimed to discover genes that contribute to ED through regulating hypoxia in corpus cavernosum smooth muscle cells (CCSMCs). METHODS: We used the Gene Expression Omnibus to acquire the sequencing data of the corpus cavernosum transcriptome for diabetic ED and nerve injury type ED rats. We intersected the common differentially expressed genes. Further verification was performed using single cell sequencing. Real-time quantitative polymerase chain reaction and immunofluorescence were used to investigate whether the differentially expressed genes are found in the corpus cavernosum. We used induced hypoxia to assess cell viability changes, and we developed a lentivirus overexpressing Cldn4 for in vitro and in vivo experiments to measure changes in JNK signaling, fibrosis, hypoxia, and erectile function. OUTCOMES: Our results indicate that targeting the JNK pathway and decreasing local hypoxia may be better options for therapeutic intervention to improve erectile function. RESULTS: We identified Cldn4 and found its expression increased in the corpora cavernosa of the 2 datasets. In addition, we found that hypoxia can increase the expression of Cldn4, activate the JNK signaling pathway, and exacerbate fibrosis in CCSMCs. Cldn4 overexpression in CCSMCs activated the JNK signaling pathway and increased fibrotic protein expression. Last, rat corpus cavernosum overexpressing Cldn4 activated the JNK signaling pathway, increased local fibrosis, and impaired erectile function. CLINICAL IMPLICATIONS: Through bioinformatics and in vitro and in vivo experiments, we found that Cldn4 has a negative effect on ED, and targeting Cldn4 may provide new ideas for ED treatment. STRENGTHS AND LIMITATIONS: Although we have identified Cldn4 as a potential target for ED treatment, we have only conducted preliminary validation on CCMSCs, and we still need to further validate in other cell lines. CONCLUSION: CCSMC hypoxia leads to increased Cldn4, in both nerve injury and diabetic ED rat models, and promotes fibrosis by activating the JNK signaling pathway.
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Disfunção Erétil , Fibrose , Sistema de Sinalização das MAP Quinases , Pênis , Masculino , Animais , Pênis/patologia , Disfunção Erétil/genética , Disfunção Erétil/etiologia , Ratos , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Ratos Sprague-Dawley , Miócitos de Músculo Liso/metabolismo , Modelos Animais de Doenças , Ereção Peniana/fisiologia , Claudinas/genética , Claudinas/metabolismoRESUMO
OBJECTIVE: To evaluate the economic value of mepolizumab as an add-on therapy to the standard of care (SoC) for patients with severe eosinophilic asthma in China. METHODS: A Markov model with three health conditions was constructed to calculate the incremental cost per quality-adjusted life year (QALY) in mepolizumab with SoC and SoC only groups from the perspective of the Chinese healthcare system throughout an entire lifespan. The model was populated with local costs, while efficacy parameters were obtained from the global Phase III MENSA trial and mortality was derived from two surveys. One-way and probabilistic sensitivity analyses were conducted. Additional scenario analysis was used to estimate the cost-effectiveness impact of changes in the price of mepolizumab. RESULTS: Over the lifetime treatment horizon, the incremental cost-effectiveness ratio (ICER) of mepolizumab plus SoC compared to SoC alone was $170 648.73 per QALY. Sensitivity analyses focused on these results. Scenario analysis showed that mepolizumab would require a price reduction of at least 82% to reach the current willingness-to-pay (WTP=$38 223.34/QALY) threshold. CONCLUSION: Mepolizumab is not a cost-effective healthcare resource in China at its current pricing.
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Antiasmáticos , Anticorpos Monoclonais Humanizados , Asma , Análise Custo-Benefício , Cadeias de Markov , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Asma/tratamento farmacológico , Asma/economia , China , Antiasmáticos/economia , Antiasmáticos/uso terapêutico , Pessoa de Meia-Idade , Masculino , Feminino , AdultoRESUMO
Squamous cell carcinoma of the head and neck (SCCHN) is a commonly detected cancer worldwide. Human papillomavirus (HPV) is emerging as an important risk factor affecting SCCHN prognosis. Therefore, identification of HPV status is essential for effective therapies in SCCHN. The aim of this study was to investigate the prognostic value of HPV-associated RNA biomarkers for SCCHN. The clinical data, survival data, and RNA-seq data of SCCHN were downloaded from The Cancer Genome Atlas database. Before the differential expression analysis, the heterogeneity between the 2 groups (HPV+ vs HPV-) of samples was analyzed using principal component analysis. The differentially expressed genes (DEGs) between HPV+ and HPV- SCCHN samples were analyzed using the R edgeR package. The Gene Ontology functional annotations, including biological process, molecular function and cellular component (CC), and Kyoto Encyclopedia of Genes And Genomes pathways enriched by the DEGs were analyzed using DAVID. The obtained matrix was analyzed by weighed gene coexpression network analysis. A total of 350 significant DEGs were identified through differential analysis, and these DEGs were significantly enriched in functions associated with keratinization, and the pathway of neuroactive ligand-receptor interaction. Moreover, 72 hub genes were identified through weighed gene coexpression network analysis. After the hub genes and DEGs were combined, we obtained 422 union genes, including 65 survival-associated genes. After regression analysis, a HPV-related prognostic model was established, which consisted of 8 genes, including Clorf105, CGA, CHRNA2, CRIP3, CTAG2, ENPP6, NEFH, and RNF212. The obtained regression model could be expressed by an equation as follows: risk scoreâ =â 0.065â ×â Clorf105â +â 0.012â ×â CGAâ +â 0.01â ×â CHRNA2â +â 0.047â ×â CRIP3â +â 0.043â ×â CTAG2-0.034â ×â ENPP6â -â 0.003â ×â NEFHâ -â 0.068â ×â RNF212. CGA interacted with 3 drugs, and CHRNA2 interacted with 11 drugs. We have identified an 8 HPV-RNA signature associated with the prognosis of SCCHN patients. Such prognostic model might serve as possible candidate biomarker and therapeutic target for SCCHN.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicações , Prognóstico , Papillomavirus Humano , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas/complicações , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/complicações , Biomarcadores , RNA , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica , LigasesRESUMO
Currently, a standardized design and calculation specification for suction drum foundations has yet to exist in China. The engineering design currently depends mainly on the subjective understanding and engineering experience of the designers, which can be considered somewhat blind and subjective. In this paper, we utilize the offshore wind power project in Yangjiang City, Guangdong Province, as our case study. Building upon domestic and international research results, relevant investigations, design specifications, and engineering applications in related fields, we conduct a systematic study on the design calculation and construction control technology of the suction drum foundation. The document presents the design calculation and inspection of the suction drum foundation. Building on this foundation, we propose a sinking feasibility analysis method and a parameter value method for the suction drum foundation calculation. We also examine the suction drum foundation construction process, examining its control parameters, technology, and standards. Finally, based on the measured data from six four-barrel guided frame platform suction drum foundations that were successfully installed, the proposed design and control method are evaluated, and their effectiveness is verified. The results of this study can provide valuable references for the design and construction of similar suction drum foundation platforms.
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ABSTRACT Introduction Swimming has high criteria for physical ability and movement by athletes. Efficient strength training can not only improve the physical training level of athletes but also increase their sports ability. Therefore, it is an important link in swimming training. Objective Explore the effect of limb strength training on athletes' fitness in swimming. Methods In this experiment, 20 swimmers majoring in physical education at a university were selected to undergo limb strength training for six weeks. Before and after the sports training, the indices such as thigh circumference, calf circumference, lower limb jumping ability, lower limb maximal strength, and lower limb balance ability of the athletes were measured, and the results of butterfly, backstroke, breaststroke, and freestyle in 50m main events were recorded. Results Efficient limb strength training can significantly promote the changes in athletes' lower limb muscle strength, improve their endurance and explosive power, improve swimmers' balance ability and movement stability, and significantly improve competitive swimming performance. Conclusion It is necessary to intensify physical strength training in athletes to improve their physical training level and economic performance. This plan can be considered very useful. Level of evidence II;Therapeutic studies - investigation of treatment outcomes.
RESUMO Introdução A natação tem elevados critérios de capacidade física e de movimentação por parte dos atletas. O treinamento de força eficiente pode não apenas melhorar o nível de treinamento físico dos atletas, mas também aumentar suas capacidades esportivas. Portanto, é um importante elo no treinamento de natação. Objetivo Explorar o efeito do treinamento de força dos membros sobre a aptidão física dos atletas na natação. Métodos Nesta experiência, 20 nadadores formados em Educação Física em uma universidade foram selecionados para realizar o treinamento de força dos membros durante seis semanas. Antes e depois do treinamento esportivo, foram medidos os índices como circunferência da coxa, circunferência da panturrilha, capacidade de saltar dos membros inferiores, força máxima dos membros inferiores e capacidade de equilíbrio dos membros inferiores dos atletas, e foram registrados os resultados de borboleta, nado de costas, nado de peito e estilo livre em eventos principais de 50m. Resultados O treinamento eficiente da força dos membros pode promover significativamente as mudanças da força muscular dos membros inferiores dos atletas, melhorar sua resistência e poder explosivo, melhorar significativamente a habilidade de equilíbrio e estabilidade de movimento dos nadadores, além de melhorar significativamente o desempenho competitivo da natação. Conclusão É necessário intensificar o treinamento de força física nos atletas, no intuito de melhorar seu nível de treinamento físico e melhorar seu desempenho econômico. Este plano pode ser considerado de grande utilidade. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.
RESUMEN Introducción La natación tiene un alto criterio de capacidad física y de movimiento por parte de los deportistas. El entrenamiento de fuerza eficiente no sólo puede mejorar el nivel de entrenamiento físico de los atletas, sino también aumentar sus capacidades deportivas. Por lo tanto, es un eslabón importante en el entrenamiento de la natación. Objetivo Explorar el efecto del entrenamiento de fuerza de las extremidades en la aptitud física de los atletas en la natación. Métodos En este experimento, se seleccionaron 20 nadadores formados en Educación Física en una universidad para realizar un entrenamiento de fuerza de las extremidades durante seis semanas. Antes y después del entrenamiento deportivo, se midieron los índices como la circunferencia del muslo, la circunferencia de la pantorrilla, la capacidad de salto de las extremidades inferiores, la fuerza máxima de las extremidades inferiores y la capacidad de equilibrio de las extremidades inferiores de los atletas, y se registraron los resultados de las pruebas principales de mariposa, espalda, nado de pecho y estilo libre en 50 metros. Resultados El entrenamiento eficaz de la fuerza de las extremidades puede promover significativamente los cambios de la fuerza muscular de las extremidades inferiores de los atletas, mejorar su resistencia y su potencia explosiva, mejorar significativamente la capacidad de equilibrio y la estabilidad del movimiento de los nadadores y mejorar significativamente el rendimiento de la natación competitiva. Conclusión Es necesario intensificar el entrenamiento de la fuerza física en los deportistas, para mejorar su nivel de entrenamiento físico y mejorar su rendimiento económico. Este plan puede considerarse de gran utilidad. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.