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The explosive amount of multi-omics data has brought a paradigm shift both in academic research and further application in life science. However, managing and reusing the growing resources of genomic and phenotype data points presents considerable challenges for the research community. There is an urgent need for an integrated database that combines genome-wide association studies (GWAS) with genomic selection (GS). Here, we present CropGS-Hub, a comprehensive database comprising genotype, phenotype, and GWAS signals, as well as a one-stop platform with built-in algorithms for genomic prediction and crossing design. This database encompasses a comprehensive collection of over 224 billion genotype data and 434 thousand phenotype data generated from >30 000 individuals in 14 representative populations belonging to 7 major crop species. Moreover, the platform implemented three complete functional genomic selection related modules including phenotype prediction, user model training and crossing design, as well as a fast SNP genotyper plugin-in called SNPGT specifically built for CropGS-Hub, aiming to assist crop scientists and breeders without necessitating coding skills. CropGS-Hub can be accessed at https://iagr.genomics.cn/CropGS/.
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Produtos Agrícolas , Bases de Dados Genéticas , Genômica , Genótipo , Fenótipo , Produtos Agrícolas/genética , Genoma , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , InternetRESUMO
'Living fossils', that is, ancient lineages of low taxonomic diversity, represent an exceptional evolutionary heritage, yet we know little about how demographic history and deleterious mutation load have affected their long-term survival and extinction risk. We performed whole-genome sequencing and population genomic analyses on Dipteronia sinensis and D. dyeriana, two East Asian Tertiary relict trees. We found large-scale genome reorganizations and identified species-specific genes under positive selection that are likely involved in adaptation. Our demographic analyses suggest that the wider-ranged D. sinensis repeatedly recovered from population bottlenecks over late Tertiary/Quaternary periods of adverse climate conditions, while the population size of the narrow-ranged D. dyeriana steadily decreased since the late Miocene, especially after the Last Glacial Maximum (LGM). We conclude that the efficient purging of deleterious mutations in D. sinensis facilitated its survival and repeated demographic recovery. By contrast, in D. dyeriana, increased genetic drift and reduced selection efficacy, due to recent severe population bottlenecks and a likely preponderance of vegetative propagation, resulted in fixation of strongly deleterious mutations, reduced fitness, and continuous population decline, with likely detrimental consequences for the species' future viability and adaptive potential. Overall, our findings highlight the significant impact of demographic history on levels of accumulation and purging of putatively deleterious mutations that likely determine the long-term survival and extinction risk of Tertiary relict trees.
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Fósseis , Endogamia , Árvores , Animais , Variação Genética , Metagenômica , Mutação , Árvores/genéticaRESUMO
Breast cancer (BC) is a prevalent cancer of the female reproductive system and a major contributor to cancer-related mortality. The activation of NLRP3, a key inflammasome, has been extensively associated with tumor-related molecular and cellular processes; however, the regulatory mechanisms and specific role of NLRP3 in breast cancer remain incompletely elucidated. This study aimed to evaluate the molecular mechanisms of NLRP3-related genes in BC. Utilizing bioinformatics methods, the present research analyzed the TCGA-BRCA dataset, which included four groups of transcriptome sequencing data as follows, normal (WT), NLRP3 knockout (KO), non-knockout-BRCA (BC-WT), and NLRP3-knockout-BRCA (BC-KO). Results indicated that NLRP3 was significantly down-regulated in TCGA-BRCA. Key module genes were mainly enriched in leukocyte cell-cell adhesion and cytokine-cytokine receptor interaction. Moreover, correlation analysis showed that NLRP3 was positively associated with cancer-associated fibroblasts and negatively associated with CD4+ Th1 T-cells. In addition, the DEGs1 and DEGs2 overlapping indicated 505 feature genes, with Chac1 (negative) and Ugt8a (positive) had the strongest correlation with differential immune cells (class-switched memory B cells). Pathway intersection revealed 13 co-KEGG pathways. The BC-KO group indicated markedly reduced levels of four genes (Ccl19, Ccl20, Ccl21a, and H2-Oa) and increased levels of two genes (Il2ra and H2-Ob). This study delved into the role of NLRP3 in BC, exploring its regulatory mechanisms and the impact gene knockout. Bioinformatics approaches identified NLRP3-associated genes, their enriched pathways, and interactions within the tumor microenvironment (TME), providing novel insights into NLRP3 function, TME dynamics, and potential targets for BC prevention and treatment.
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Neoplasias da Mama , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Humanos , Feminino , Transcriptoma , Regulação Neoplásica da Expressão GênicaRESUMO
As an important protein encoded by hepatitis B virus (HBV), HBV X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). It has been shown that seven in absentia homologue 1 (SIAH1) could regulates the degradation of HBx through the ubiquitin-proteasome pathway. However, as a member of SIAH family, the regulatory effects of SIAH2 on HBx remain unclear. In this study, we first confirmed that SIAH2 could reduce the protein levels of HBx depending on its E3 ligase activity. Moreover, SIAH2 interacted with HBx and induced its K48-linked polyubiquitination and proteasomal degradation. Furthermore, we provided evidence that SIAH2 inhibits HBx-associated HCC cells proliferation by regulating HBx. In conclusion, our study identified a novel role for SIAH2 in promoting HBx degradation and SIAH2 exerts an inhibitory effect in the proliferation of HBx-associated HCC through inducing the degradation of HBx. Our study provides a new idea for the targeted degradation of HBx and may have great huge significance into providing novel evidence for the targeted therapy of HBV-infected HCC.
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Carcinoma Hepatocelular , Proliferação de Células , Vírus da Hepatite B , Neoplasias Hepáticas , Proteínas Nucleares , Proteólise , Proteínas Proto-Oncogênicas c-jun , Transativadores , Ubiquitina-Proteína Ligases , Ubiquitinação , Proteínas Virais Reguladoras e Acessórias , Humanos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Linhagem Celular Tumoral , Células Hep G2 , Vírus da Hepatite B/metabolismo , Vírus da Hepatite B/patogenicidade , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Transdução de Sinais , Transativadores/metabolismo , Transativadores/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Proteínas Virais Reguladoras e Acessórias/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismoRESUMO
Hypoxic-ischemic brain damage (HIBD) in the perinatal period is an important cause of cerebral damage and long-term neurological sequelae, and can place much pressure on families and society. Our previous study demonstrated that miRNA-326 reduces neuronal apoptosis by up-regulating the δ-opioid receptor (DOR) under oxygen-glucose deprivation in vitro. In the present study, we aimed to explore the neuroprotective effects of the miRNA-326/DOR axis by inhibiting apoptosis in HIBD using neonatal miRNA-326 knockout mice. Neonatal C57BL/6 mice, neonatal miRNA-326 knockout mice, and neonatal miRNA-326 knockout mice intraperitoneally injected with the DOR inhibitor naltrindole were treated with hypoxic-ischemia (HI). Neurological deficit scores, magnetic resonance imaging, terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling, and Caspase-3, Bax, and B-cell lymphoma 2 (Bcl-2) expression were evaluated on day 2 after HI. Neurobehavioral analyses were performed on days 2 and 28 after HI. Additionally, the Morris water maze test was conducted on days 28. Compared with HI-treated neonatal C57BL/6 mice, HI-treated neonatal miRNA-326 knockout mice had higher neurological deficit scores, smaller cerebral infarction areas, and improved motor function, reaction ability, and long-term spatial learning and memory. These effects were likely the result of inhibiting apoptosis; the DOR inhibitor reversed these neuroprotective effects. Our findings indicate that miRNA-326 knockout plays a neuroprotective effect in neonatal HIBD by inhibiting apoptosis via the target gene DOR.
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Animais Recém-Nascidos , Apoptose , Hipóxia-Isquemia Encefálica , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs , Receptores Opioides delta , Animais , Masculino , Camundongos , Apoptose/genética , Hipóxia-Isquemia Encefálica/genética , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Fármacos Neuroprotetores/farmacologia , Receptores Opioides delta/genética , Receptores Opioides delta/metabolismoRESUMO
As a non-collinear expression form of genetic information, chimeric RNAs increase the complexity of transcriptome in diverse organisms. Although chimeric RNAs have been identified in plants, few common features have been revealed. Here, we systemically explored the landscape of chimeric RNAs across multi-accession and multi-tissue using pan-genome and transcriptome data of four plants: rice, maize, soybean, and Arabidopsis. Among the four species, conserved characteristics of breakpoints and parental genes were discovered. In each species, chimeric RNAs displayed a high level of diversity among accessions, and the clustering of accessions using chimeric events was generally concordant with clustering based on genomic variants, implying a general relationship between genetic variations and chimeric RNAs. Through mass spectrometry, we confirmed a fusion protein OsNDC1-OsGID1L2 and observed its subcellular localization, which differed from the original proteins. Phenotypic cues in transgenic rice suggest the potential functions of OsNDC1-OsGID1L2. Moreover, an intriguing chimeric event Os01g0216500-Os01g0216900, generated by a large deletion in basmati rice, also exists in another accession without the deletion, demonstrating its convergence in evolution. Our results illuminate the characteristics and hint at the evolutionary implications of plant chimeric RNAs, which serve as a supplement to genetic variations, thus expanding our understanding of genetic diversity.
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Arabidopsis , Glycine max , Oryza , Zea mays , Oryza/genética , Oryza/metabolismo , Arabidopsis/genética , Zea mays/genética , Zea mays/metabolismo , Glycine max/genética , Glycine max/metabolismo , RNA de Plantas/genética , Variação Genética , Plantas Geneticamente Modificadas/genética , Transcriptoma/genética , Genoma de Planta/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Cancer remains a leading cause of global mortality. The tumor microbiota has increasingly been recognized as a key regulator of cancer onset and progression, in addition to shaping tumor responses to immunotherapy. Microbes, including viruses, bacteria, fungi, and other eukaryotic species can impact the internal homeostasis and health of humans. Research focused on the gut microflora and the intratumoral microbiome has revolutionized the current understanding of how tumors grow, progress, and resist therapeutic interventions. Even with this research, however, there remains relatively little that is known with respect to the abundance of microbes and their effects on tumors and the tumor microenvironment. Engineered exosomes are a class of artificial extracellular nanovesicles that can actively transport small molecule drugs and nucleic acids, which have the broad prospects of tumor cell therapy. The present review offers an overview of recent progress and challenges associated with the intratumoral microbiome and engineered exosomes in the context of cancer research. These discussions are used to inform the construction of a novel framework for engineered exosome-mediated targeted drug delivery, taking advantage of intratumoral microbiota diversity as a strategic asset and thereby providing new opportunities to more effectively treat and manage cancer in the clinic.
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Exossomos , Microbiota , Neoplasias , Humanos , Exossomos/metabolismo , Neoplasias/terapia , Neoplasias/microbiologia , Neoplasias/imunologia , Animais , Sistemas de Liberação de MedicamentosRESUMO
BACKGROUND: The clinical routine test of HBV-specific T cell reactivity is still limited due to the high polymorphisms of human leukocyte antigens (HLA) in patient cohort and the lack of universal detection kit, thus the clinical implication remains disputed. METHODS: A broad-spectrum peptide library, which consists of 103 functionally validated CD8+ T-cell epitopes spanning overall HBsAg, HBeAg, HBx and HBpol proteins and fits to the HLA polymorphisms of Chinese and Northeast Asian populations, was grouped into eight peptide pools and was used to establish an ELISpot assay for enumerating the reactive HBV-specific T cells in PBMCs. Totally 294 HBV-infected patients including 203 ones with chronic hepatitis B (CHB), 13 ones in acute resolved stage (R), 52 ones with liver cirrhosis (LC) and 26 ones with hepatocellular carcinoma (HCC) were detected, and 33 CHB patients were longitudinally monitored for 3 times with an interval of 3-5 months. RESULTS: The numbers of reactive HBV-specific T cells were significantly correlated with ALT level, HBsAg level, and disease stage (R, CHB, LC and HCC), and R patients displayed the strongest HBV-specific T cell reactivity while CHB patients showed the weakest one. For 203 CHB patients, the numbers of reactive HBV-specific T cells presented a significantly declined trend when the serum viral DNA load, HBsAg, HBeAg or ALT level gradually increased, but only a very low negative correlation coefficient was defined (r = - 0.21, - 0.21, - 0.27, - 0.079, respectively). Different Nucleotide Analogs (NUCs) did not bring difference on HBV-specific T cell reactivity in the same duration of treatment. NUCs/pegIFN-α combination led to much more reactive HBV-specific T cells than NUCs monotherapy. The dynamic numbers of reactive HBV-specific T cells were obviously increasing in most CHB patients undergoing routine treatment, and the longitudinal trend possess a high predictive power for the hepatitis progression 6 or 12 months later. CONCLUSION: The presented method could be developed into an efficient reference method for the clinical evaluation of cellular immunity. The CHB patients presenting low reactivity of HBV-specific T cells have a worse prognosis for hepatitis progression and should be treated using pegIFN-α to improve host T-cell immunity.
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Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Biblioteca de Peptídeos , Epitopos de Linfócito T/uso terapêutico , Cirrose Hepática , DNA ViralRESUMO
Understanding how life history shapes genetic diversity is a fundamental issue in evolutionary biology, with important consequences for conservation. However, we still have an incomplete picture of the impact of life history on genome-wide patterns of diversity, especially in long-lived semelparous plants. Puya raimondii is a high-altitude semelparous species from the Andes that flowers at 40-100 years of age. We sequenced the whole genome and estimated the nucleotide diversity of 200 individuals sampled from nine populations. Coalescent-based approaches were then used to infer past population dynamics. Finally, these results were compared with results obtained for the iteroparous species, Puya macrura. The nine populations of P. raimondii were highly divergent, highly inbred, and carried an exceptionally high genetic load. They are genetically depauperate, although, locally in the genome, balancing selection contributed to the maintenance of genetic polymorphism. While both P. raimondii and P. macrura went through a severe bottleneck during the Pleistocene, P. raimondii did not recover from it and continuously declined, while P. macrura managed to bounce back. Our results demonstrate the importance of life history, in particular generation time and reproductive strategy, in affecting population dynamics and genomic variation, and illustrate the genetic fragility of long-lived semelparous plants.
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Variação Genética , Genoma de Planta , Genética Populacional , Fatores de Tempo , Dinâmica PopulacionalRESUMO
BACKGROUND AND PURPOSE: Ir192 vaginal brachytherapy (IBT) is commonly used for patients with postoperative endometrial cancer (EC). We devised a novel multichannel vaginal applicator that could be equipped with an electronic brachytherapy (EBT) device. We aimed to explore the differences in physical parameters between the EBT and IBT. MATERIALS AND METHODS: This retrospective study included 20 EC patients who received adjuvant IBT from March 1, 2023, to May 1, 2023. Multichannel vaginal cylinders were used, and three-dimensional plans were generated. We designed an electronic multichannel vaginal applicator model and simulated a three-dimensional EBT plan. In order to ensure comparability, D90 of the CTV for the EBT plan was normalized to be equivalent to that of the IBT plan for the same patient. RESULTS: Twenty EBT plans were compared with 20 IBT plans. Results showed, the mean D90 value of clinical target volume (CTV) was 536.1 cGy for both treatment plans. For the mean dose of CTV, the EBT was significantly greater (738.3 vs. 684.3 cGy, p = 0.000). There was no significant difference in CTV coverage between the EBT and IBT plans. For high-dose areas (V200% and V150%), the EBTs were significantly greater. There were no significant differences in the maximum doses to the vaginal mucosa between the EBT and IBT, whether at the apex or in the middle segment. For the bladder and rectum, both the low-dose area and high-dose area were significantly lower in the EBT plans. For the conformity index, there was no significant difference between the EBT and IBT plans. For the dose homogeneity index, the EBT value was lower. CONCLUSION: In conclusion, under the premise of a three-dimensional brachytherapy plan, for patients receiving multichannel vaginal applicator brachytherapy, compared with IBT, EBT could reduce the dose to the surrounding organs at risk while maintaining the dose in the target area.
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Braquiterapia , Neoplasias do Endométrio , Radioisótopos de Irídio , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Humanos , Feminino , Braquiterapia/métodos , Braquiterapia/instrumentação , Neoplasias do Endométrio/radioterapia , Neoplasias do Endométrio/patologia , Estudos Retrospectivos , Radioisótopos de Irídio/uso terapêutico , Planejamento da Radioterapia Assistida por Computador/métodos , Pessoa de Meia-Idade , Idoso , Radiometria , Órgãos em Risco/efeitos da radiaçãoRESUMO
BACKGROUND: In patients undergoing breast-conserving therapy without surgical clip implantation, the accuracy of tumor bed identification and the consistency of clinical target volume (CTV) delineation under computed tomography (CT) simulation remain suboptimal. This study aimed to investigate the feasibility of implementing preoperative magnetic resonance (MR) simulation on delineations by assessing interobserver variability (IOV). METHODS: Preoperative MR and postoperative CT simulations were performed in patients who underwent breast-conserving surgery with no surgical clips implanted. Custom immobilization pads were used to ensure the same supine position. Three radiation oncologists independently delineated the CTV of tumor bed on the images acquired from MR and CT simulation registration and CT simulation alone. Cavity visualization score (CVS) was assigned to each patient based on the clarity of the tumor bed on CT simulation images. IOV was indicated by generalized conformity index (CIgen), denoted as CIgen-CT and CIgen-MR/CT, and the distance between the centroid of mass (dCOM), denoted as dCOMCT and dCOMMR/CT. The variation of IOV in different CVS subgroups was analyzed. RESULTS: A total of 10 patients were enrolled in this study. The median and interquartile range (IQR) of maximum pathological diameter of the tumors in all patients were 1.55 (0.80-1.92) cm. No statistical significance was found between the volumes of CTVs on CT simulation and on MR/CT simulation registration images (p = 0.387). CIgen-MR/CT was significantly larger than CIgen-CT (p = 0.005). dCOMMR/CT was significantly smaller than dCOMCT (p = 0.037). The median and IQR of CVS in all patients were 2.34 (2.00-3.08). The difference of CIgen between CIgen-MR/CT and CIgen-CT was larger in the low CVS group (p = 0.016). The difference of dCOM showed a decreasing trend when CVS was lower, although it did not reach statistical significance (p = 0.095). CONCLUSIONS: For patients who underwent breast-conserving surgery without surgical clip implantation, the use of preoperative MR simulation in delineating the CTV of tumor bed decreased the IOV among observers. The consistency of tumor bed identification was improved especially in cases where the margins of tumor bed were challenging to visualize on CT simulation images. The study findings offer potential benefits in reducing local recurrence and minimizing tissue irritation in the surrounding areas. Future investigation in a larger patient cohort to validate our results is warranted.
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Neoplasias da Mama , Imageamento por Ressonância Magnética , Mastectomia Segmentar , Variações Dependentes do Observador , Tomografia Computadorizada por Raios X , Humanos , Feminino , Neoplasias da Mama/cirurgia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Mastectomia Segmentar/métodos , Projetos Piloto , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Idoso , Adulto , Cuidados Pré-Operatórios/métodos , Carga Tumoral , Estudos de Viabilidade , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
Chronic pain is a common and challenging clinical problem that significantly impacts patients' quality of life. The sodium channel Nav1.8 plays a crucial role in the occurrence and development of chronic pain, making it one of the key targets for treating chronic pain. In this article, we combined virtual screening with cell membrane chromatography techniques to establish a novel method for rapid high-throughput screening of selective Nav1.8 inhibitors. Using this approach, we identified a small molecule compound 6, which not only demonstrated high affinity and inhibitory activity against Nav1.8 but also exhibited significant inhibitory effects on CFA-induced chronic inflammatory pain. Compared to the positive drug VX-150, compound 6 showed a more prolonged analgesic effect, making it a promising candidate as a Nav1.8 inhibitor with potential clinical applications. This discovery provides a new therapeutic option for the treatment of chronic pain.
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Analgésicos , Canal de Sódio Disparado por Voltagem NAV1.8 , Sulfonamidas , Analgésicos/farmacologia , Analgésicos/química , Analgésicos/síntese química , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/síntese química , Animais , Humanos , Canal de Sódio Disparado por Voltagem NAV1.8/metabolismo , Relação Estrutura-Atividade , Benzenossulfonamidas , Estrutura Molecular , Camundongos , Relação Dose-Resposta a Droga , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/química , Bloqueadores do Canal de Sódio Disparado por Voltagem/síntese químicaRESUMO
Two X-ray scintillators based on organic-inorganic hybrids were constructed by judiciously incorporating lanthanide cations and organic ligands within a single material. The obtained Eu-pba and Tb-pba not only feature excellent radiation, hydrolytic, and thermal stabilities but also exhibit a linear response to the X-ray dose rate with detection limits of 4.92 and 3.17 µGy s-1, respectively. We further present a flexible scintillator film fabricated by embedding Tb-pba in a polydimethylsiloxane (PDMS) polymer. Their incorporation enables X-ray imaging with a spatial resolution of approximately 10 lp mm-1. These results emphasize the potential of lanthanide organic-inorganic hybrids to achieve outstanding performance in X-ray scintillation and imaging.
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AIMS: A few studies have reported the effect and safety of pulsed field ablation (PFA) catheters for ablating atrial fibrillation (AF), which were mainly based on basket-shaped or flower-shaped designs. However, the clinical application of a circular-shaped multi-electrode catheter with magnetic sensors is very limited. To study the efficacy and safety of a PFA system in patients with paroxysmal AF using a circular-shaped multi-electrode catheter equipped with magnetic sensors for pulmonary vein isolation (PVI). METHODS AND RESULTS: A novel proprietary bipolar PFA system was used for PVI, which utilized a circular-shaped multi-electrode catheter with magnetic sensors and allowed for three-dimensional model reconstruction, mapping, and ablation in one map. To evaluate the efficacy, efficiency, and safety of this PFA system, a prospective, multi-centre, single-armed, pre-market clinical study was performed. From July 2021 to December 2022, 151 patients with paroxysmal AF were included and underwent PVI. The study examined procedure time, immediate success rate, procedural success rate at 12 months, and relevant complications. In all 151 patients, all the pulmonary veins were acutely isolated using the studied system. Pulsed field ablation delivery was 78.4 ± 41.8 times and 31.3 ± 16.7â ms per patient. Skin-to-skin procedure time was 74.2 ± 29.8â min, and fluoroscopy time was 13.1 ± 7.6â min. The initial 11 (7.2%) cases underwent procedures with deep sedation anaesthesia, and the following cases underwent local anaesthesia. In the initial 11 cases, 4 cases (36.4%) presented transient vagal responses, and the rest were all successfully preventatively treated with atropine injection and rapid fluid infusion. No severe complications were found during or after the procedure. During follow-up, 3 cases experienced atrial flutter, and 11 cases had AF recurrence. The estimated 12-month Kaplan-Meier of freedom from arrhythmia was 88.4%. CONCLUSION: The PFA system, comprised of a circular PFA catheter with magnetic sensors, could rapidly achieve PVI under three-dimensional guidance and demonstrated excellent safety with comparable effects.
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Veias Pulmonares/cirurgia , Resultado do Tratamento , Estudos Prospectivos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Catéteres , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Fenômenos Magnéticos , RecidivaRESUMO
BACKGROUND: Fine particulate matter (PM2.5) is a recognized risk factor for respiratory and cardiovascular diseases, but the association between PM2.5 and rheumatoid arthritis (RA) is still controversial. Additionally, evidence on the relationship of green space with RA is scarce. This study aimed to investigate the separate and combined associations of PM2.5 and green space with risk of RA. METHODS: Our study involved 30,684 participants from the Yinzhou cohort in Ningbo, China. PM2.5 concentrations were determined using a land-use regression model. Residential green space was assessed using the Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) from satellite images. We employed the Cox proportional hazard model to evaluate the relationships of PM2.5 and green space with RA. RESULTS: During the 176,894 person-years of follow-up period, 354 cases of RA were identified. Hazard ratio (HR) and the corresponding 95% confidence interval (95% CI) for every interquartile range (IQR) increase in PM2.5 were 1.23 (95% CI: 1.02, 1.49). Compared with lower exposure to residential green space, individuals living in areas with more green space had a decreased risk of RA (HR was 0.80 (95% CI: 0.70, 0.92), 0.80 (95% CI: 0.70, 0.92), and 0.79 (95% CI: 0.70, 0.89) for 250m, 500m, and 1000m NDVI buffers, respectively). Similar results were observed for the association between EVI and RA. Furthermore, a significant multiplicative interaction was observed between PM2.5 and green space (NDVI 250m and EVI 250m). No mediating effect of PM2.5 on the relationship between green space and RA was observed. CONCLUSION: Our findings indicated that living in areas with higher green space was linked to a reduced risk of RA, whereas living in areas with higher PM2.5 was associated with an increased risk of RA. The beneficial effect of high green space may be offset by exposure to PM2.5.
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BACKGROUND: Air pollution and outdoor light at night (LAN) have been reported to be related to type 2 diabetes (T2D). However, their interaction with risk of T2D remains uncertain. Therefore, our study aimed to explore the relationship between outdoor LAN, air pollution and incident T2D. METHODS: Our study included a cohort of 24,147 subjects recruited from 2015 to 2018 in Ningbo, China. Land use regression models were used to evaluate particulate matter with a diameter ≤2.5 µm (PM2.5), ≤10 µm (PM10) and nitrogen dioxide (NO2). Satellite images data with a spatial resolution of 500m was used to estimate outdoor LAN levels. T2D new cases were identified by medical records based on health information system. Cox proportional hazards models were used to estimate Hazard ratios (HRs) and 95% confidence intervals (CIs). Moreover, we investigated the multiplicative and additive interactions between air pollution and outdoor LAN. RESULTS: During 108,908 person-years of follow-up period, 1016 T2D incident cases were identified. The HRs (95% CIs) were 1.22 (1.15, 1.30) for outdoor LAN, 1.20 (1.00, 1.45) for PM2.5, 1.23 (1.11, 1.35) for PM10 and 1.19 (1.04, 1.37) for NO2 in every interquartile range increase, respectively. Furthermore, significant interactions were observed between outdoor LAN and NO2. CONCLUSIONS: Our findings indicated that air pollution and outdoor LAN were positively associated with T2D. Moreover, we observed an interaction between outdoor LAN and NO2 suggesting that stronger associations for outdoor LAN and T2D in areas with higher levels of NO2, and for NO2 and T2D in areas with higher levels of outdoor LAN.
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Early and differential diagnosis of sepsis is essential to avoid unnecessary antibiotic use and further reduce patient morbidity and mortality. Here, we aimed to identify predictors of sepsis and advance a machine-learning strategy to predict sepsis-induced respiratory tract infection (RTI). Patients with sepsis and RTI were selected via retrospective analysis, and essential population characteristics and laboratory parameters were recorded. To improve the performance of the primary model and avoid over-fitting, a recursive feature elimination with cross-validation (RFECV) strategy was used to screen the optimal subset of biomarkers and construct nine machine-learning models based on this subset; the average accuracy, precision, recall, and F1-score were used for evaluation of the models. We identified 430 patients with sepsis and 686 patients with RTI. A total of 39 features were collected, with 23 features identified for initial model construction. Using the RFECV algorithm, we found that the XGBoost classifier, which only needed to include seven biomarkers, demonstrated the best performance among all prediction models, with an average accuracy of 89.24 ± 2.28, while the Ridge classifier, which included 11 biomarkers, had an average accuracy of only 83.87 ± 4.69. The remaining models had prediction accuracies greater than 88%. We developed nine models for predicting sepsis using a strategy that combined RFECV with machine learning. Among these models, the XGBoost classifier, which included seven biomarkers, showed the best performance and highest accuracy for predicting sepsis and may be a promising tool for the timely identification of sepsis.
Assuntos
Algoritmos , Biomarcadores , Aprendizado de Máquina , Infecções Respiratórias , Sepse , Humanos , Sepse/diagnóstico , Sepse/sangue , Biomarcadores/sangue , Infecções Respiratórias/diagnóstico , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PURPOSE: This study evaluates the performance of a kilovoltage x-ray image-guidance system equipped with a novel post-processing optimization algorithm on the newly introduced TAICHI linear accelerator (Linac). METHODS: A comparative study involving image quality tests and radiation dose measurements was conducted across six scanning protocols of the kV-cone beam computed tomography (CBCT) system on the TAICHI Linac. The performance assessment utilized the conventional Feldkamp-Davis-Kress (FDK) algorithm and a novel Non-Local Means denoising and adaptive scattering correction (NLM-ASC) algorithm. Image quality metrics, including spatial resolution, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR), were evaluated using a Catphan 604 phantom. Radiation doses for low-dose and standard protocols were measured using a computed tomography dose index (CTDI) phantom, with comparative measurements from the Halcyon Linac's iterative CBCT (iCBCT). RESULTS: The NLM-ASC algorithm significantly improved image quality, achieving a 300%-1000% increase in CNR and SNR over the FDK-only images and it also showed a 100%-200% improvement over the iCBCT images from Halcyon's head protocol. The optimized low-dose protocols yielded higher image quality than the standard FDK protocols, indicating potential for reduced radiation exposure. Clinical implementation confirmed the TAICHI system's utility for precise and adaptive radiotherapy. CONCLUSION: The kV-IGRT system on the TAICHI Linac, with its novel post-processing algorithm, demonstrated superior image quality suitable for routine clinical use, effectively reducing image noise without compromising other quality metrics.
RESUMO
Wetlands, as core habitats for supporting waterbird diversity, provide a variety of ecosystem services through diverse ecosystem functioning. Wetland degradation and wetland-habitat loss undermine the relationship between biodiversity-ecosystem functioning (BEF), affecting the diversity of habitats and waterbirds. The conservation of waterbird diversity is closely linked to the proper functioning of wetland ecosystems (nutrient cycling, energy storage, and productivity). Waterbirds have complex habitat preferences and sensitivities, which affect biotic interactions. By highlighting the importance of temporal and spatial scales guided by BEF, a habitat-waterbird conservation framework is presented (BEF relationships are described at three levels: habitat, primary producers, and waterbird diversity). We present a novel perspective on habitat conservation for waterbirds by incorporating research on the effects of biodiversity and ecosystem functioning to address the crucial challenges in global waterbird diversity loss, ecosystem degradation, and habitat conservation. Last, it is imperative to prioritize strategies of habitat protection with the incorporation of BEF for future waterbird conservation.
Assuntos
Ecossistema , Áreas Alagadas , Conservação dos Recursos Naturais , Biodiversidade , CiclismoRESUMO
BACKGROUND: Spinal anaesthesia is a common anaesthetic method for caesarean sections but often results in hypotension, posing potential risks to maternal and neonatal health. Norepinephrine, as a vasopressor, may be effective in preventing and treating this hypotension. This systematic review and meta-analysis aims to systematically evaluate the efficacy and safety of prophylactic norepinephrine infusion for the treatment of hypotension following spinal anaesthesia in caesarean sections. METHODS: Literature searches were conducted in PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP databases for relevant studies on prophylactic administration of norepinephrine for the treatment of hypotension after spinal anaesthesia in caesarean delivery. Reference lists of included articles were also searched. The latest search update was on March 20, 2024. Meta-analysis was conducted using R software. The methods recommended by the Cochrane Handbook, Begge's and Egger's tests were used for risk of bias evaluation of the included literature. RESULTS: Nine studies were finally included in this study. The results showed that prophylactic administration of norepinephrine was superior to the control group in four aspects of treating hypotension after spinal anaesthesia in caesarean delivery: the incidence of hypotension was reduced [RR = 0.34, 95%CI (0.27-0.43), P < 0.01]; the incidence of severe hypotension was reduced [RR = 0.32, 95%CI (0.21-0.51), P < 0.01]; and maternal blood pressure was more stable with MDPE [MD = -5.00, 95%CI (-7.80--2.21), P = 0.06] and MDAPE [MD = 4.11, 95%CI (1.38-6.85), P < 0.05], the incidence of nausea and vomiting was reduced [RR = 0.52, 95%CI (0.35-0.77), P < 0.01]. On the other hand, the incidence of reactive hypertension was higher than the control group [RR = 3.58, 95%CI (1.94-6.58), P < 0.01]. There was no difference between the two groups in one aspects: newborn Apgar scores [MD = -0.01, 95%CI (-0.10-0.09, P = 0.85)]. CONCLUSION: Prophylactic administration of norepinephrine is effective in treating hypotension after spinal anaesthesia in caesarean delivery patients; however, it does not provide improved safety and carries a risk of inducing reactive hypertension.
Hypotension, or low blood pressure, after spinal anaesthesia can threaten the health of both mothers and their babies during caesarean sections. Norepinephrine is a drug that affects heart rate less and does not easily cross the placental barrier, which may reduce its potential negative effects on the baby. However, there are not many studies on using norepinephrine as a preventive measure. Our study systematically evaluated the use of prophylactic norepinephrine infusion to prevent hypotension in caesarean section patients. We found that it is effective in preventing low blood pressure but does not show improved safety and carries some risk of causing high pressure as a reaction.