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BACKGROUND: Few studies have investigated the association between gestational age, birth weight, and esophageal cancer risk; however, causality remains debated. We aimed to establish causal links between genetic gestational age and birth weight traits and gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and esophageal adenocarcinoma (EA). Additionally, we explored if known risk factors mediate these links. AIM: To analyze of the relationship between gestational age, birth weight and GERD, BE, and EA. METHODS: Genetic data on gestational age and birth weight (n = 84689 and 143677) from the Early Growth Genetics Consortium and outcomes for GERD (n = 467253), BE (n = 56429), and EA (n = 21271) from genome-wide association study served as instrumental variables. Mendelian randomization (MR) and mediation analyses were conducted using MR-Egger, weighted median, and inverse variance weighted methods. Robustness was ensured through heterogeneity, pleiotropy tests, and sensitivity analyses. RESULTS: Birth weight was negatively correlated with GERD and BE risk [odds ratio (OR) = 0.78; 95% confidence interval (CI): 0.69-0.8] and (OR = 0.75; 95%CI: 0.60-0.9), respectively, with no significant association with EA. No causal link was found between gestational age and outcomes. Birth weight was positively correlated with five risk factors: Educational attainment (OR = 1.15; 95%CI: 1.01-1.31), body mass index (OR = 1.06; 95%CI: 1.02-1.1), height (OR = 1.12; 95%CI: 1.06-1.19), weight (OR = 1.13; 95%CI: 1.10-1.1), and alcoholic drinks per week (OR = 1.03; 95%CI: 1.00-1.06). Mediation analysis showed educational attainment and height mediated the birth weight-BE link by 13.99% and 5.46%. CONCLUSION: Our study supports the protective role of genetically predicted birth weight against GERD, BE, and EA, independent of gestational age and partially mediated by educational attainment and height.
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Sponges are the most basal metazoan phylum1 and may have played important roles in modulating the redox architecture of Neoproterozoic oceans2. Although molecular clocks predict that sponges diverged in the Neoproterozoic era3,4, their fossils have not been unequivocally demonstrated before the Cambrian period5-8, possibly because Precambrian sponges were aspiculate and non-biomineralized9. Here we describe a late-Ediacaran fossil, Helicolocellus cantori gen. et sp. nov., from the Dengying Formation (around 551-539 million years ago) of South China. This fossil is reconstructed as a large, stemmed benthic organism with a goblet-shaped body more than 0.4 m in height, with a body wall consisting of at least three orders of nested grids defined by quadrate fields, resembling a Cantor dust fractal pattern. The resulting lattice is interpreted as an organic skeleton comprising orthogonally arranged cruciform elements, architecturally similar to some hexactinellid sponges, although the latter are built with biomineralized spicules. A Bayesian phylogenetic analysis resolves H. cantori as a crown-group sponge related to the Hexactinellida. H. cantori confirms that sponges diverged and existed in the Precambrian as non-biomineralizing animals with an organic skeleton. Considering that siliceous biomineralization may have evolved independently among sponge classes10-13, we question the validity of biomineralized spicules as a necessary criterion for the identification of Precambrian sponge fossils.
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Fósiles , Poríferos , Animales , Teorema de Bayes , China , Filogenia , Poríferos/anatomía & histología , Poríferos/clasificaciónRESUMEN
Previous studies have indicated that tire wear particles (TWPs) leachate exposure induced serious eye injury in fish through inhibiting the thyroid peroxidase (TPO) enzyme activity. However, the main TPO inhibitors in the leachate were still unknown. In this study, we identified 2-Mercaptobenzothiazole (MBT) as the potential TPO inhibitor in the TWPs leachate through references search, model prediction based on Danish QSAR and ToxCast database, molecular docking, and in vivo assay. We further explored the toxic mechanism of MBT under environmentally relevant concentrations. The decreased eye size of zebrafish larvae was mainly caused by the decreased lens diameter and cell density in the inner nuclear layer (INL) and outer nuclear layer (ONL) of the retina. Transcriptomics analysis demonstrated that the eye phototransduction function was significantly suppressed by inhibiting the photoreceptor cell proliferation process after MBT exposure. The altered opsin gene expression and decreased opsin protein levels were induced by weakening thyroid hormone signaling after MBT treatment. These results were comparable to those obtained from a known TPO inhibitor, methimazole. This study has identified MBT as the primary TPO inhibitor responsible for inducing eye impairment in zebrafish larvae exposed to TWPs leachate. It is crucial for reducing the toxicity of TWPs leachate in fish.
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Contaminantes Químicos del Agua , Pez Cebra , Animales , Contaminantes Químicos del Agua/toxicidad , Goma , Lesiones Oculares/inducido químicamente , Lesiones Oculares/patología , Benzotiazoles , Yoduro Peroxidasa/metabolismo , Yoduro Peroxidasa/genética , Simulación del Acoplamiento Molecular , Retina/efectos de los fármacos , Larva/efectos de los fármacosRESUMEN
Epoxiconazole (EPX) is a world widely used chiral triazole fungicide in the agriculture field. The excessive application of this triazole may cause damage to lizards. However, limited information is known about the toxicokinetics of EPX on lizards. Our study aimed to investigate the enantioselective absorption, distribution, metabolism, and elimination (ADME) of EPX in lizards following low and high dose exposure (10 and 100 mg kg-1 bodyweitht (bw)). The results demonstrated that (+)-EPX was easier absorbed than (-)-EPX in lizard plasma. Both (+)-EPX and (-)-EPX were detected in the liver, gonad, kidney, skin, brain, and intestine, with (+)-EPX preferentially distributed in these tissues. The elimination of (-)-EPX was faster than that of (+)-EPX in lizard liver and kidney in the high dose groups. Chiral conversion was found between EPX enantiomers in lizard skin. Simultaneously, five metabolites including M2, M4, M10, M18 and M19 were detected in lizard liver and kidney after EPX enantiomers exposure. The relative concentrations of M2, M4, and M10 were higher in the liver and kidney of (-)-EPX groups than those produced from (+)-EPX groups. The metabolic enzymes CYP3A4 and SULT1A1 primarily mediated enantioselective metabolism of EPX. The conclusions drawn from this study significantly enhance our understanding of the enantioselective behaviors of chiral triazole fungicides in reptiles, offering essential guidance for assessing the risks associated with different enantiomers of triazole fungicides.
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Compuestos Epoxi , Fungicidas Industriales , Lagartos , Triazoles , Animales , Triazoles/química , Triazoles/toxicidad , Triazoles/metabolismo , Lagartos/metabolismo , Fungicidas Industriales/química , Fungicidas Industriales/metabolismo , Compuestos Epoxi/metabolismo , Compuestos Epoxi/química , Estereoisomerismo , Hígado/metabolismo , Riñón/metabolismo , Masculino , Distribución TisularRESUMEN
Microplastic pollution in the soil environment has received extensive attention, but the effects of different land use patterns on the sub-watershed scale on soil microplastic pollution are poorly understood. The Luoshijiang sub-watershed in the north of Erhai Lake was selected as the research object, and the characteristics of microplastic pollution in farmland, riparian zone, grassland, and woodland soils were analyzed. The pollution risks of microplastics in the four types of soil were assessed using the polymer risk index method, and the effects of land use patterns on the distribution and risk of microplastic pollution were further explored. The results showed that:â The abundance of microplastics in the soil of the Luoshijiang sub-watershed ranged from 220 to 1 900 n·kg-1, and the average abundance was (711 ± 55) n·kg-1. The main polymer types were polyester (PES, 32.52%) and polyethylene terephthalate (PET, 21.95%). The particle size of microplastics was concentrated in the range of 0.5-2 mm (61.89%). Fiber was the main shape of microplastics (>75%), and the dominant color was transparent (58.50%). â¡ Land use patterns determined the abundance and pollution characteristics of soil microplastics in the Luoshijiang sub-watershed. A significantly higher abundance of microplastics was found in the soil of farmland[(885 ± 95) n·kg-1] and riparian zone[(837 ± 155) n·kg-1], which had stronger intensities of human activity, than that in woodland soil[(491 ± 53) n·kg-1] (P<0.05). Film and fragment microplastics mainly occurred in farmland soil, which also had the largest number of polymer types and the most abundant colors. ⢠The risk index level of microplastics (Level â ¢) in the soil of farmland was higher than that of the other three land use patterns (Level â ). This research indicated that the higher the intensity of human activities of a sub-watershed was, the more complex the occurrence characteristics of soil microplastics, the richer the types of polymers, and the higher the potential pollution risks would be. Therefore, it is necessary to strengthen the control of soil microplastic pollution in farmland.
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OBJECTIVE: This study synthesizes evidence from the Loughborough Passing Test to evaluate the short-passing ability of soccer players and summarizes the reported variables that affect this ability to provide support for the development and improvement of short-passing abilities in soccer players. METHODS: In this systematic review using the PRISMA guidelines, a comprehensive search was conducted in Web of Science, PubMed, and EBSCOhost from inception to July 2023 to identify relevant articles from the accessible literature. Only studies that used the Loughborough test to assess athletes' short-passing ability were included. The quality of the included studies was independently assessed by two reviewers using the PEDro scale, and two authors independently completed the data extraction. RESULTS: Based on the type of intervention or influencing factor, ten studies investigated training, nine studies investigated fatigue, nine studies investigated supplement intake, and five studies investigated other factors. CONCLUSION: Evidence indicates that fitness training, small-sided games training, and warm-up training have positive effects on athletes' short-passing ability, high-intensity special-position training and water intake have no discernible impact, mental and muscular exhaustion have a significantly negative effect, and the effect of nutritional ergogenic aid intake is not yet clear. Future research should examine more elements that can affect soccer players' short-passing ability. TRIAL REGISTRATION: https://inplasy.com/ ., identifier: INPLASY20237.
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RGB-T salient object detection (SOD) has made significant progress in recent years. However, most existing works are based on heavy models, which are not applicable to mobile devices. Additionally, there is still room for improvement in the design of cross-modal feature fusion and cross-level feature fusion. To address these issues, we propose a lightweight cross-modal information mutual reinforcement network for RGB-T SOD. Our network consists of a lightweight encoder, the cross-modal information mutual reinforcement (CMIMR) module, and the semantic-information-guided fusion (SIGF) module. To reduce the computational cost and the number of parameters, we employ the lightweight module in both the encoder and decoder. Furthermore, to fuse the complementary information between two-modal features, we design the CMIMR module to enhance the two-modal features. This module effectively refines the two-modal features by absorbing previous-level semantic information and inter-modal complementary information. In addition, to fuse the cross-level feature and detect multiscale salient objects, we design the SIGF module, which effectively suppresses the background noisy information in low-level features and extracts multiscale information. We conduct extensive experiments on three RGB-T datasets, and our method achieves competitive performance compared to the other 15 state-of-the-art methods.
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OBJECTIVES: This study aims to gain insight into each attribute as presented in the value of implantable medical devices, quantify attributes' strength and their relative importance, and identify the determinants of stakeholders' preferences. METHODS: A mixed-methods design was used to identify attributes and levels reflecting stakeholders' preference toward the value of implantable medical devices. This design combined literature reviewing, expert's consultation, one-on-one interactions with stakeholders, and a pilot testing. Based on the design, six attributes and their levels were settled. Among 144 hypothetical profiles, 30 optimal choice sets were developed, and healthcare professionals (decision-makers, health technology assessment experts, hospital administrators, medical doctors) and patients as stakeholders in China were surveyed. A total of 134 respondents participated in the survey. Results were analyzed by mixed logit model and conditional logit model. RESULTS: The results of the mixed logit model showed that all the six attributes had a significant impact on respondents' choices on implantable medical devices. Respondents were willing to pay the highest for medical devices that provided improvements in clinical safety, followed by increased clinical effectiveness, technology for treating severe diseases, improved implement capacity, and innovative technology (without substitutes). CONCLUSIONS: The findings of DCE will improve the current evaluation on the value of implantable medical devices in China and provide decision-makers with the relative importance of the criteria in pricing and reimbursement decision-making of implantable medical devices.
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Prioridad del Paciente , Prótesis e Implantes , Humanos , Encuestas y Cuestionarios , Resultado del Tratamiento , China , Conducta de ElecciónRESUMEN
Preventing soil nitrogen (N) losses driven by microbial nitrification and denitrification contributes to improving global environmental concerns caused by NO3--N leaching and N2O emission. Quorum sensing (QS) signals regulate nitrification and denitrification of N-cycling bacteria in pure culture and water treatment systems, and mediate the composition of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in activated sludge. However, whether disrupting QS could prevent soil N losses remains unclear. This study explored the feasibility of applying quorum sensing inhibitors (QSIs) as an innovative strategy to reduce N losses from agricultural soils. The two QSIs, penicillic acid and 4-iodo-N-[(3S)-tetrahydro-2-oxo-3-furanyl]-benzeneacetamide (4-iodo PHL), were more effective in reducing N losses than traditional inhibitors, including N-(n-butyl) thiophosphoric triamide and 3,4-dimethylpyrazole phosphate. After 36 days of aerobic incubation, penicillic acid and 4-iodo PHL inhibited nitrification by 39% and 68%, respectively. The inhibitory effects are attributed to the fact that 4-iodo PHL decreased the abundance of archaeal and bacterial amoA genes, as well as the relative abundance of Candidatus Nitrocosmicus (AOA), Candidatus Nitrososphaera (AOA), and Nitrospira (nitrite-oxidizing bacteria/comammox), while penicillic acid reduced archaeal amoA abundance and the relative abundance of Nitrosospira (AOB) and the microbes listed above. Penicillic acid also strongly inhibited denitrification (33%) and N2O emissions (61%) at the peak of N2O production (day 4 of anaerobic incubation) via decreasing nitrate reductase gene (narG) abundance and increasing N2O reductase gene (nosZ) abundance, respectively. Furthermore, the environmental risks of QSIs to microbial community structure and network stability, CO2 emissions, and soil animals were acceptable. Overall, QSIs have application potential in agriculture to reduce soil N losses and the associated effect on climate change. This study established a new method to mitigate N losses from the perspective of QS, and can serve as important basis of decreasing the environmental risks of agricultural non-point source pollution.
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Betaproteobacteria , Suelo , Animales , Suelo/química , Nitrógeno , Amoníaco , Ácido Penicílico , Percepción de Quorum , Microbiología del Suelo , Bacterias/genética , Archaea , Oxidación-ReducciónRESUMEN
RNA interference (RNAi) has been proposed as a promising strategy for sustainable and ecofriendly pest control. The insect cuticle lipids were deposited on the body surface and functioned as a defense against chemical xenobiotics. They consisted of aliphatic compounds, including free fatty acids (FFAs). However, elongase of very long chain fatty acids (ELOs) is essential for FFA biosynthesis; the function of ELO is still unknown in many arthropods, including Panonychus citri (P. citri). In this study, three ELOs were cloned. Developmental-specific mRNA expression results revealed that three PcELOs were highly expressed in egg and adult females. Whereas PcELO7 was dominantly expressed in adult females. Under spirobudiclofen stress, ELOs mRNA expression had different changes, and PcELO7 was down-regulated. The silencing of PcELO7 resulted in a dramatic reduction of oviposition and hatchability. Significant reduction of FFA contents was also examined within PcELO7-repressed P. citri. In addition, we found that PcELO7 mRNA levels were related to fecundity and could affect triacylglycerol (TG) contents. The findings demonstrated that the introduction of dsPcELO7 via oral feeding induced the RNA interference-mediated silencing of a special target gene and could result in mortality and reproduction. In conclusion, PcELO7 is a special RNAi target for P. citri control, and its lethal mechanism might be disturbing lipids biosynthesis.
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Tetranychidae , Animales , Femenino , Tetranychidae/genética , Elongasas de Ácidos Grasos/metabolismo , Fertilidad/genética , ARN Mensajero/metabolismo , LípidosRESUMEN
OBJECTIVES: The China sports lottery contributes to sports and welfare causes. This study aims to construct a macro forecasting model supporting its sustained growth aligned with Vision 2035. METHODS: The modeling employed a distributional regression. Sales data of the China sports lottery from 2011 to 2022 were chosen as the response variable, alongside various macro- and event-level explanatory factors. RESULTS: A gamma distribution best fit the data. In the stable model spanning 2011-2019, urbanization, population dynamics, and FIFA emerged as significant contributors (Chi-square p < 0.05) to the location shift parameter. These three factors retained their significance in the 2011-2022 shock model, where shock itself notably impacted sales (p < 0.001). Utilizing the shock model, we simulated the trajectory of the China sports lottery up to 2035. China's demographics changes are poised to create structural headwinds starting in 2026, leading to an anticipated decline in sales driven by population shifts from 2032 onward. However, the FIFA effect is projected to continue fortifying this sector. CONCLUSIONS: Beyond offering original insights into the sales trajectory until 2035, specifically concerning new urbanization, negative population growth, and the FIFA effect, this macro forecasting framework can assist in addressing the policy priority of balancing growth with risk mitigation. We recommend policymakers connect market development with mass sports, potentially garnering a dual boost from the growing population of older consumers and the inherent benefits of a "FIFA (mass sports)" effect. A people-centered approach to the China sports lottery could significantly contribute to the long-range objectives of achieving common prosperity outlined in Vision 2035.
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Deportes , Urbanización , Humanos , China , Dinámica Poblacional , Crecimiento DemográficoRESUMEN
This study explored the potential of methanol as a sustainable feedstock for biomanufacturing, focusing on Methylobacterium extorquens, a well-established representative of methylotrophic cell factories. Despite this bacterium's long history, its untapped photosynthetic capabilities for production enhancement have remained unreported. Using genome-scale flux balance analysis, it was hypothesized that introducing photon fluxes could boost the yield of 3-hydroxypropionic acid (3-HP), an energy- and reducing equivalent-consuming chemicals. To realize this, M. extorquens was genetically modified by eliminating the negative regulator of photosynthesis, leading to improved ATP levels and metabolic activity in non-growth cells during a two-stage fermentation process. This modification resulted in a remarkable 3.0-fold increase in 3-HP titer and a 2.1-fold increase in its yield during stage (II). Transcriptomics revealed that enhanced light-driven methanol oxidation, NADH transhydrogenation, ATP generation, and fatty acid degradation were key factors. This development of photo-methylotrophy as a platform technology introduced novel opportunities for future production enhancements.
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Ácido Láctico/análogos & derivados , Methylobacterium , Methylobacterium/genética , Methylobacterium/metabolismo , Fermentación , Metanol/metabolismo , Adenosina Trifosfato/metabolismo , Ingeniería Metabólica/métodosRESUMEN
In biological control programs, knowledge about diapause regulation in natural enemy insects provides important insight for improving long-term storage, transportation, and field adoption of these biological control agents. As a natural predator of agricultural pests, the lady beetle Coccinella septempunctata has been commercially mass-cultured and widely employed in pest management. In some insects, insulin signaling, in conjunction with the downstream transcription factor Forkhead box O (FoxO), are master regulators of multiple physiological processes involved in diapause, but it is unclear whether insulin signaling and FoxO affect the diapause of C. septempunctata. In this study, we use a combination of approaches to demonstrate that insulin signaling and FoxO mediate the diapause response in C. septempunctata. In diapausing beetles, application of exogenous insulin and knocking down expression of CsFoxo with RNA interference (RNAi) both rescued beetles from developmental arrest. In non-diapausing beetles, knocking down expression of the insulin receptor (CsInR) with RNA interference (RNAi) arrested ovarian development and decreased juvenile hormone (JH) content to levels comparable to the diapause state. Taken together, these results suggest that a shutdown of insulin signaling prompts the activation of the downstream FoxO gene, leading to the diapause phenotype.
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Escarabajos , Diapausa , Humanos , Animales , Escarabajos/genética , Insulina/metabolismo , Factores de Transcripción Forkhead/metabolismo , Transducción de SeñalRESUMEN
A major subtype of renal cancer is clear cell renal cell carcinoma (ccRCC). Krüppel-like factor 3 (KLF3) dysfunction is also revealed leading to poor prognosis in multiple cancer types. However, dysregulation and molecular dynamics of KLF3 underlying ccRCC progression still remains elusive. Here KLF3 gene and protein expressions in ccRCC were explored using data cohorts from The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Clinical Proteomic Tumor Analysis Consortium (CPTAC) and verified them in our patient cohort. Correlations of KLF3 expression with clinicopathological features, epigenetic modification, and immune microenvironment characteristics were further investigated. KLF3 was significantly down-regulated expressed in ccRCC tissues compared to adjacent normal controls. Adverse pathological parameters and poor prognosis were associated with lower expression of KLF3. Mechanically, KLF3 regulation was mainly attributed to CpG island methylation. KLF3-high expression subgroup was significantly enriched in cell signaling pathways most associated with EMT markers, angiogenesis, inflammatory response, apoptosis, TGF-ß, degradation of ECM, G2M checkpoint, and PI3K-AKT-mTOR. Based on GDSC database, KLF3 upregulation was identified to be associated with higher sensitivities towards PI3K-Akt-mTOR pathway inhibitors such as PI-103, PIK-93, and OSI-027. In addition, patients with down-regulated KLF3 expressions were found more sensitive towards Trametinib, Cetuximab, and Erlotinib. Collectively, our findings suggest that KLF3 may act as a suitable biomarker for prognosis prediction, tumor microenvironment (TME) phenotype identification, thereby helping ccRCC patients to make better therapeutic decisions.
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Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Pronóstico , Fosfatidilinositol 3-Quinasas , Proteómica , Proteínas Proto-Oncogénicas c-akt , Neoplasias Renales/genética , Serina-Treonina Quinasas TOR , Factores de Transcripción de Tipo Kruppel/genética , Microambiente TumoralRESUMEN
Spodoptera frugiperda, one of the most destructive corn pests in the world, invaded China in December 2018. In this study, sublethal concentrations (LC10 and LC30) of emamectin benzoate (EB) were used to treat pesticide-free treatment (PFT) and EB treatment (ET) of S. frugiperda. In PFT, compared with the control (CK), the pupal weight, hatching rate, and pupation rate of LC10 and LC30 groups were significantly reduced. The fecundity and the expression of vitellogenin gene (SfVg) were decreased after LC30 treatment, while the LC10 treatment groups showed no significant difference from the control group. In ET, compared to CK, the fecundity was increased by 11.14 and 18.8%. The expression of SfVg was upregulated by 2.6 times after LC30 treatment. Moreover, RNAi-mediated SfVg knockdown resulted in a nearly 70% reduction in oviposition. The result provided a theoretical basis for optimizing the application of EB and Vg-dsRNA in the control of S. frugiperda.
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Insecticidas , Plaguicidas , Animales , Femenino , Spodoptera , Vitelogeninas/genética , Interferencia de ARN , Reproducción , Plaguicidas/farmacología , Larva , Insecticidas/toxicidadRESUMEN
Blocking programmed cell death protein 1 (PD-1) is an effective therapeutic strategy for melanoma. However, patients often develop tumor recurrence postoperatively due to the low response rate to the anti-PD-1 antibody (aPD-1). In this study, we developed an in situ sprayable fibrin gel that contains cytosine-guanine oligodeoxynucleotides (CpG ODNs)-modified ovalbumin (OVA) antigen-expressing bone marrow dendritic cell (DC)-derived small extracellular vesicles (DC-sEVs) and aPD-1. CpG ODNs can activate DCs, which have potent immunostimulatory effects, by stimulating both the maturation and activation of tumor-infiltrating dendritic cells (TIDCs) and DCs in tumor-draining lymph nodes (TDLNs). In addition, DC-sEVs can deliver OVA to the same DCs, leading to the specific expression of tumor antigens by antigen-presenting cells (APCs). In brief, the unique synergistic combination of aPD-1 and colocalized delivery of immune adjuvants and tumor antigens enhances antitumor T-cell immunity, not only in the tumor microenvironment (TME) but also in TDLNs. This effectively attenuates local tumor recurrence and metastasis. Our results suggest that dual activation by CpG ODNs prolongs the survival of mice and decreases the recurrence rate in an incomplete tumor resection model, providing a promising approach to prevent B16-F10-OVA melanoma tumor recurrence and metastasis.
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Melanoma Experimental , Recurrencia Local de Neoplasia , Humanos , Animales , Ratones , Inmunoterapia/métodos , Melanoma Experimental/terapia , Antígenos de Neoplasias , Oligodesoxirribonucleótidos/uso terapéutico , Células Dendríticas , Ratones Endogámicos C57BL , Microambiente TumoralRESUMEN
OBJECTIVE: Pancreatic cancer is a digestive malignancy with dismal prognosis. The advent of Heidelberg TRIANGLE dissection technique brings a turning point to improve the chance of survival. Our study aimed to evaluated the cost-effectiveness of open pancreaticoduodenectomy (OPD) versus OPD combined with TRIANGLE operation (OPD-TRIANGLE) for patients with pancreatic cancer from the perspective of healthcare system in China. METHODS: Two hundred forty-six patients with pancreatic cancer who underwent OPD or OPD-TRIANGLE from January to September 2022 were enrolled in this study. We performed a decision tree model to assess clinical and economic implications of different surgical strategies. Estimation of health utilities was based on published literature, while costs were acquired from the hospitals, clinical expert consultations, and other local charge. The incremental cost-effectiveness ratio (ICER) was regarded as the primary outcome. Uncertainty of the findings was addressed via sensitivity analyses and scenario analyses. RESULTS: The results indicated that OPD-TRIANGLE group yielded additional 0.0402 QALYs at an incremental cost of US$1501.83 compared with OPD group, and the corresponding ICER was US$37,358.96 per QALY. The probabilities of OPD-TRIANGLE as the prior option were 52.8% at the WTP threshold of 60,000 US$/QALY. The main factors lined with costs incorporating total medical costs and operation-related costs. With 5-20% price reduction of OPD-TRIANGLE, the outcomes were also economically attractive. CONCLUSION: The findings of this population-based study suggested that OPD-TRIANGLE was likely to be cost-effective for patients with pancreatic cancer when compared against OPD. Further in-depth studies should be conducted to provide more comprehensive evidence.
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Neoplasias Pancreáticas , Pancreaticoduodenectomía , Humanos , Análisis Costo-Beneficio , Pancreaticoduodenectomía/métodos , Neoplasias Pancreáticas/cirugía , Pancreatectomía , China/epidemiología , Neoplasias PancreáticasRESUMEN
Autism is a neurodevelopmental condition involving atypical sensory-perceptual functions together with language and socio-cognitive deficits. Previous work has reported subtle alterations in the asymmetry of brain structure and reduced laterality of functional activation in individuals with autism relative to non-autistic individuals (NAI). However, whether functional asymmetries show altered intrinsic systematic organization in autism remains unclear. Here, we examined inter- and intra-hemispheric asymmetry of intrinsic functional gradients capturing connectome organization along three axes, stretching between sensory-default, somatomotor-visual, and default-multiple demand networks, to study system-level hemispheric imbalances in autism. We observed decreased leftward functional asymmetry of language network organization in individuals with autism, relative to NAI. Whereas language network asymmetry varied across age groups in NAI, this was not the case in autism, suggesting atypical functional laterality in autism may result from altered developmental trajectories. Finally, we observed that intra- but not inter-hemispheric features were predictive of the severity of autistic traits. Our findings illustrate how regional and patterned functional lateralization is altered in autism at the system level. Such differences may be rooted in atypical developmental trajectories of functional organization asymmetry in autism.
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Trastorno del Espectro Autista , Trastorno Autístico , Conectoma , Humanos , Imagen por Resonancia Magnética , Encéfalo , Lateralidad Funcional/fisiología , Mapeo EncefálicoRESUMEN
An important aspect of environmental pollution, lead contamination is a widespread problem in several ecosystems. The present study aimed to evaluate the potential effects of low concentration lead stress on the development and reproduction of Aleuroglyphus ovatus. They were fed with artificial diet containing four different concentrations of lead (12.5, 25, 50, and 100 mg/kg). The results showed that there were both accelerating effect of lead (at low concentrations), as well as retarding effects (at high concentrations) on the development of the mite, and lead stress significantly prolonged the immature stages of A. ovatus and this inhibitory effect was greater with greater lead concentrations. The immature stages in the L group were shorter than those in the S group. In the S and L groups, the oviposition periods were significantly longer in the treatments with lower lead concentrations than in the control, while they were significantly shorter in those treatments of higher lead concentrations. Age-specific survival rate (lx) started to decline earlier in the S group, whereas there were no differences between the L group and CK. Age-specific fecundity rate (mx) peaked earlier in the S group than in CK, while mx peaked later in L1 and L2 than in CK. The rm value and net reproduction rate (R0) of treated A. ovatus decreased with increasing lead concentrations. Lower lead concentrations could promote population expansion while higher concentrations could inhibit population size. These results confirmed the developmental effect of lead stress on A. ovatus, highlighting that heavy metal contamination has negative effects on organisms in their natural environment.