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Acute myocardial infarction (AMI) is triggered by the blockage of coronary arteries, leading to restricted blood flow to the myocardium, which results in damage and cell death. While the traditional understanding of cell death primarily revolves around apoptosis, a new player in the game has emerged: ferroptosis. This novel form of cell death relies on iron and is propelled by reactive oxygen species (ROS). Lipid metabolism, an indispensable physiological process, plays a vital role in preserving cellular homeostasis. However, when this metabolic pathway is disrupted, the accumulation of excess waste increases, specifically lipid peroxides, which are strongly linked to the occurrence and progression of AMI. As a result, comprehending this complex interaction between ferroptosis and lipid metabolism could pave the way for new therapeutic approaches in tackling AMI.
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Interfacial self-assembly is a well-established method for the preparation of a two-dimensional (2D) metal nanofilm from nanoscale building blocks. However, the as-prepared nanofilm exhibits limited conductivity because of the large contact resistance at the junctions among its building blocks. Here, we report a salt-assisted, in situ current nanowelding strategy to weld an interfacial Au nanoparticle (NP) film for downstream applications, such as high-performance electrocatalysts. Particularly, we found that salt-assisted interfacial assembly can reduce the size of the nanogaps among neighboring Au NPs and, in turn, greatly improve the conductivity of the resultant Au NP film. Consequently, the Au NP film can be readily welded using current, and the welding extent can be monitored in real-time by looking at the passing current. The welding finally produces a nanoporous Au film (NPGF) with a network nanostructure, high conductivity, and abundant active sites so that it delivers a large current density of 86.96 µA·cm-2 (1.81 times higher than that from the pristine Au NP film) and shows improved cycling stability for methanol electrooxidation. Thus, these results offer a low-cost, solution-processable approach for the fabrication of a large-area, interconnected nanofilm from nanoscale building blocks beyond Au NPs, which may find diverse downstream applications.
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PURPOSE OF REVIEW: The purpose of this literature review was to determine if medications used to treat osteoporosis are also effective for treating osteoarthritis (OA). RECENT FINDINGS: A total of 40 relevant articles were identified. Studies were categorized into those (1) discussing estrogen and selective estrogen receptor modulators (SERMs), (2) bisphosphonates, (3) parathyroid hormone (PTH) analogs, and (4) denosumab, and (5) prior review articles. A large amount of evidence suggests that estrogen and SERMs are effective at reducing OA symptoms and disease progression. Evidence suggests that bisphosphonates, the most common medications used to treat osteoporosis, can reduce OA symptoms and disease progression. In vivo studies suggest that PTH analogs may improve the cartilage destruction associated with OA; however, few human trials have examined its use for OA. Denosumab is approved to treat osteoporosis, bone metastases, and certain types of breast cancer, but little study has been done with respect to its effect on OA. The current evidence indicates that medications used to treat osteoporosis are also effective for treating OA. Estrogen, SERMs, and bisphosphonates have the most potential as OA therapies. Less is known regarding the effectiveness of PTH analogs and denosumab in OA, and more research is needed.
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Conservadores da Densidade Óssea , Denosumab , Difosfonatos , Progressão da Doença , Osteoartrite , Osteoporose Pós-Menopausa , Moduladores Seletivos de Receptor Estrogênico , Humanos , Osteoartrite/tratamento farmacológico , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Difosfonatos/uso terapêutico , Denosumab/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Hormônio Paratireóideo/uso terapêutico , Estrogênios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Teriparatide, a recombinant parathyroid hormone, is pivotal in osteoporosis treatment, particularly in post-surgical recovery for hip fractures. This study investigates its efficacy in functional recovery post-hip fracture surgery in elderly patients, a demographic particularly susceptible to osteoporotic fractures. METHODS: In this retrospective cohort study, 150 elderly patients with proximal femoral fractures undergoing open reduction and internal fixation were enrolled. They were categorized into two groups: receiving 20 µg of daily teriparatide injections for 18 months and receiving standard antiresorptive medications during a 24-month follow-up. Detailed records of patient demographics, Fracture Risk Assessment Tool scores, and comorbidities were kept. Key outcomes, including bone mineral density (BMD) and functional scores (Barthel Index and Visual Analog Scale for hip pain), were evaluated at 3 and 24 months post-surgery. RESULTS: Out of the original cohort, 126 patients (20 men and 106 women with an average age of 85.5 ± 9.3 years) completed the study. The teriparatide group exhibited significant enhancements in both functional scores and BMD when compared to the control group. Notably, functional improvements were less pronounced in male patients compared to female patients. Additionally, the incidence of new fractures was markedly lower in the teriparatide group. CONCLUSION: Administering teriparatide daily for 18 months post-surgery for proximal femoral fractures significantly benefits very elderly patients by improving functionality and bone density, with observed differences in recovery between genders. These results reinforce the efficacy of teriparatide as a potent option for treating osteoporosis-related fractures in the elderly and highlight the importance of considering gender-specific treatment and rehabilitation strategies.
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Fraturas do Quadril , Osteoporose , Fraturas Proximais do Fêmur , Idoso , Feminino , Humanos , Masculino , Idoso de 80 Anos ou mais , Teriparatida/uso terapêutico , Densidade Óssea , Estudos Retrospectivos , Fraturas do Quadril/cirurgia , Osteoporose/complicações , Osteoporose/tratamento farmacológicoRESUMO
BACKGROUND: Femoral neck fractures in older adult patients are a major concern and often necessitate surgical intervention. This study compared the clinical outcomes of 2 surgical techniques: the femoral neck system (FNS) and cannulated compression screws (CCSs). METHODS: A total of 40 female patients (mean age 73.50 ± 11.55 years) with femoral neck fractures of Pauwels classification type II and receiving surgical fixation between 2020 and 2022 were enrolled. The patients were categorized into an FNS group (n = 12) or a CCS group (n = 28), and surgical duration, intraoperative blood loss, length of hospital stay, and incidence of postoperative adverse events were analyzed. RESULTS: No significant intergroup differences in demographic characteristics were discovered. The mean surgical duration for all patients was 52.88 ± 22.19 min, with no significant difference between the groups. However, the FNS group experienced significantly higher intraoperative blood loss (P = 0.002) and longer hospital stay (P = 0.023) than did the CCS group. The incidence of osteonecrosis was higher in the CCS group, whereas the incidence of nonunion or malunion was higher in the FNS group. The surgical method did not appear to be a significant risk factor. The main risk factor for revision surgery was longer duration until the first adverse event (P = 0.015). CONCLUSION: The FNS does not appear to provide superior surgical outcomes compared with CCSs in older adult women with Pauwels classification type II femoral neck fractures. A longer duration between surgical fixation and the first adverse event before stabilization of the fracture site may be a risk factor for revision surgery.
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Fraturas do Colo Femoral , Necrose da Cabeça do Fêmur , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Colo do Fêmur , Perda Sanguínea Cirúrgica , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Fraturas do Colo Femoral/cirurgia , Fraturas do Colo Femoral/etiologia , Necrose da Cabeça do Fêmur/etiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Pelvic girdle pain (PGP) is a common problem during pregnancy and postpartum and negatively affects women's well-being. Yet it is not well known in China. This study assessed PGP's intensity, location, and quality and the status of daily activities on postpartum women with pain, and explored the relationship between pain and the prevalence of depressive symptoms. A cross-sectional study recruiting 1,038 eligible women at 6 weeks postpartum from the obstetric clinic of a hospital was conducted in Beijing, China. Data were collected using self-reported questionnaires, including Introductory information form, Body chart, Number Rating Scale, McGill Pain Questionnaire-2, Pelvic Girdle Questionnaire, and Edinburgh Postnatal Depression Scale. In this study, 32.2 percent women experienced pain. The mean (SD) pain intensity score was 3.07 ± 1.60. About 50.6 percent women experienced sacroiliac joint pain, and 25.5 percent women experienced pain in a combination of locations. About 73.1 percent women experienced aching pain, and 57.5 percent experienced more than one kind of pain quality. The mean total score, which assesses activity and symptom limitations, was 21.93 ± 17.35 (percent), of which a normal sex life (1.29 ± 0.94) was made more challenging due to pain. In mental health, the prevalence of depressive symptoms coincided with the prevalence of pain (p = 0.008). Postpartum PGP still needs to be taken seriously, and women with pain require further support. The above knowledge offers information to manage pain, daily lives and depressive symptoms, contributes to think about strategies to better promote postpartum women physical and mental health in the future.
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Atividades Cotidianas , Medição da Dor , Dor da Cintura Pélvica , Período Pós-Parto , Humanos , Feminino , Período Pós-Parto/psicologia , Adulto , Dor da Cintura Pélvica/epidemiologia , Dor da Cintura Pélvica/psicologia , Estudos Transversais , Inquéritos e Questionários , China/epidemiologia , Prevalência , Pequim/epidemiologia , Gravidez , Qualidade de Vida , Depressão/epidemiologia , Depressão/psicologia , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/psicologia , Adulto JovemRESUMO
BACKGROUND: Accumulated evidence highlights the significance of the crosstalk between epigenetic and epitranscriptomic mechanisms, notably 5-methylcytosine (5mC) and N6-methyladenosine (m6A). Herein, we conducted a widespread analysis regarding the crosstalk between 5mC and m6A regulators in hepatocellular carcinoma (HCC). METHODS: Pan-cancer genomic analysis of the crosstalk between 5mC and m6A regulators was presented at transcriptomic, genomic, epigenetic, and other multi-omics levels. Hub 5mC and m6A regulators were summarized to define an epigenetic and epitranscriptomic module eigengene (EME), which reflected both the pre- and post-transcriptional modifications. RESULTS: 5mC and m6A regulators interacted with one another at the multi-omic levels across pan-cancer, including HCC. The EME scoring system enabled to greatly optimize risk stratification and accurately predict HCC patients' clinical outcomes and progression. Additionally, the EME accurately predicted the responses to mainstream therapies (TACE and sorafenib) and immunotherapy as well as hyper-progression. In vitro, 5mC and m6A regulators cooperatively weakened apoptosis and facilitated proliferation, DNA damage repair, G2/M arrest, migration, invasion and epithelial-to-mesenchymal transition (EMT) in HCC cells. The EME scoring system was remarkably linked to potential extrinsic and intrinsic immune escape mechanisms, and the high EME might contribute to a reduced copy number gain/loss frequency. Finally, we determined potential therapeutic compounds and druggable targets (TUBB1 and P2RY4) for HCC patients with high EME. CONCLUSIONS: Our findings suggest that HCC may result from a unique synergistic combination of 5mC-epigenetic mechanism mixed with m6A-epitranscriptomic mechanism, and their crosstalk defines therapeutic response and pharmacogenomic landscape.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , 5-Metilcitosina , Apoptose , Farmacogenética , Linhagem Celular Tumoral , Pontos de Checagem da Fase G2 do Ciclo Celular , Progressão da DoençaRESUMO
We propose a fast and robust method for calibrating Spatial Light Modulators (SLMs) based on polarization phase-shifting interferometry. Our method effectively calibrates the SLM by addressing both the static aberration and nonlinear phase response, utilizing specially designed gray images loaded sequentially onto the SLM. Notably, we introduce a novel kinoform that effectively eliminates the influence of tilt phase shift between two shots of the polarization camera. This results in a highly accurate phase aberration map and phase modulation curve with exceptional stability, making it an ideal method to calibrate the SLM with exceptional efficiency and precision in real applications.
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Accurate and sensitive analysis of p53 DNA is important for early diagnosis of cancer. In this work, a fluorescence sensing system based on DNA supersandwich nanowires and cation exchange (CX)-triggered multiplex signal amplification was constructed for the detection of p53 DNA. In the presence of p53 DNA, the DNA self-assembles to form a DNA supersandwich nanowire that generates long double-stranded DNA. Subsequently, the cation exchange (CX) reaction between ZnS and Ag+ was utilized to release free Zn2+. With the participation of Zn2+, DNAzyme catalyzes the hydrolysis of numerous catalytic molecular beacons, resulting in a greatly enhanced fluorescence signal due to the cycling of DNAzyme. The fluorescence values increased in proportion to the concentrations of p53 DNA in the range of 10 pM to 200 nM, and a detection limit (LOD) of 2.34 pM (S/N = 3) was obtained. This method provides an effective strategy for the quantitative detection of p53 DNA.
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The development of a gas sensor capable of detecting ammonia with high selectivity and rapid response at room temperature has consistently posed a formidable challenge. To address this issue, the present study utilized a one-step solvothermal method to co-assemble α-Fe2O3 and SnO2 by evenly covering SnO2 nanoparticles on the surface of α-Fe2O3. By controlling the morphology and Fe/Sn mole ratio of the composite, the as-prepared sample exhibits high-performance detection of NH3. At room temperature conditions, a gas sensor composed of α-Fe2O3@3%SnO2 demonstrates a rapid response time of 14 s and a notable sensitivity of 83.9% when detecting 100 ppm ammonia. Experiments and density functional theory (DFT) calculations suggest that the adsorption capacity of α-Fe2O3 to ammonia is enhanced by the surface effect provided by SnO2. Meanwhile, the existence of SnO2 tailors the pore structure and effective surface area of α-Fe2O3, creating multiple channels for the diffusion and adsorption of ammonia molecules. Additionally, an N-N heterostructure is formed between α-Fe2O3 and SnO2, which enhances the potential energy barrier and improves the ammonia sensing performance. Demonstration experiments have proved that the sensor shows significant advantages over commercial sensors in the process of ammonia detection in agricultural facilities. This work provides new insights into the perspectives on ammonia detection at room temperature.
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TPN171 is a novel phosphodiesterase-5 (PDE5) inhibitor used to treat pulmonary arterial hypertension (PAH) and erectile dysfunction (ED), which currently is undergoing phase II clinical trials in China. In this single-center, single-dose, nonrandomized, and open design study, radiolabeled [14C]TPN171 was used to investigate the metabolic mechanism, pharmacokinetic characteristics, and clearance pathways of TPN171 in 6 healthy Chinese male volunteers. Each volunteer was administered a single oral suspension of 10 mg (100 µCi) of [14C]TPN171. We found that TPN171 was absorbed rapidly in humans with a peak time (Tmax) of 0.667 h and a half-life (t1/2) of approximately 9.89 h in plasma. Excretion of radiopharmaceutical-related components was collected 216 h after administration, accounting for 95.21% of the dose (46.61% in urine and 48.60% in feces). TPN171 underwent extensive metabolism in humans. Twenty-two metabolites were detected in human plasma, urine, and feces using a radioactive detector combined with a high-resolution mass spectrometer. According to radiochromatograms, a glucuronide metabolite of O-dealkylated TPN171 exceeded 10% of the total drug-related components in human plasma. However, according to the Food and Drug Administration (FDA) guidelines, no further tests are needed to evaluate the safety of this metabolite because it is a phase II metabolite, but the compound is still worthy of attention. The main metabolic biotransformation of TPN171 was mono-oxidation (hydroxylation and N-oxidation), dehydrogenation, N-dealkylation, O-dealkylation, amide hydrolysis, glucuronidation, and acetylation. Cytochrome P450 3A4 (CYP3A4) mainly catalyzed the formation of metabolites, and CYP2E1 and CYP2D6 were involved in the oxidative metabolism of TPN171 to a lesser extent. According to the incubation data, M1 was mainly metabolized to M1G by UDP-glucuronosyltransferase 1A9 (UGT1A9), followed by UGT1A7 and UGT1A10.
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Inibidores da Fosfodiesterase 5 , Hipertensão Arterial Pulmonar , Humanos , Masculino , Inibidores da Fosfodiesterase 5/uso terapêutico , Pirimidinonas , Biotransformação , Fezes , Administração OralRESUMO
For sample size calculation in clinical trials with survival endpoints, the logrank test, which is the optimal method under the proportional hazard (PH) assumption, is predominantly used. In reality, the PH assumption may not hold. For example, in immuno-oncology trials, delayed treatment effects are often expected. The sample size without considering the potential violation of the PH assumption may lead to an underpowered study. In recent years, combination tests such as the maximum weighted logrank test have received great attention because of their robust performance in various hazards scenarios. In this paper, we propose a flexible simulation-free procedure to calculate the sample size using combination tests. The procedure extends the Lakatos' Markov model and allows for complex situations encountered in a clinical trial, like staggered entry, dropouts, etc. We evaluate the procedure using two maximum weighted logrank tests, one projection-type test, and three other commonly used tests under various hazards scenarios. The simulation studies show that the proposed method can achieve the target power for all compared tests in most scenarios. The combination tests exhibit robust performance under correct specification and misspecification scenarios and are highly recommended when the hazard-changing patterns are unknown beforehand. Finally, we demonstrate our method using two clinical trial examples and provide suggestions about the sample size calculations under nonproportional hazards.
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Neoplasias , Projetos de Pesquisa , Humanos , Modelos de Riscos Proporcionais , Tamanho da Amostra , Simulação por Computador , Análise de SobrevidaRESUMO
Selection pressures driven by natural causes or human interference are key factors causing genome variants and signatures of selection in specific regions of the genome. Gamecocks were bred for cockfighting, presenting pea-combs, larger body sizes, stronger limbs, and higher levels of aggression than other chickens. In this study, we aimed to explore the genomic differences between Chinese gamecocks and commercial, indigenous, foreign, and cultivated breeds by detecting the regions or sites under natural or artificial selection using genome-wide association studies (GWAS), genome-wide selective sweeps based on the genetic differentiation index (FST), and transcriptome analyses. Ten genes were identified using GWAS and FST: gga-mir-6608-1, SOX5, DGKB, ISPD, IGF2BP1, AGMO, MEOX2, GIP, DLG5, and KCNMA1. The ten candidate genes were mainly associated with muscle and skeletal development, glucose metabolism, and the pea-comb phenotype. Enrichment analysis results showed that the differentially expressed genes between the Luxi (LX) gamecock and Rhode Island Red (RIR) chicken were mainly related to muscle development and neuroactive-related pathways. This study will help to understand the genetic basis and evolution of Chinese gamecocks and support the further use of gamecocks as an excellent breeding material from a genetic perspective.
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Galinhas , Estudo de Associação Genômica Ampla , Transcriptoma , Animais , Galinhas/genética , Perfilação da Expressão Gênica , Genômica , Polimorfismo de Nucleotídeo Único , Seleção GenéticaRESUMO
Lead pollution has increasingly become the focus of environmental pollution, which is a great harm to the ecological environment and human health. Strict control of the emission of lead pollutants and accurate monitoring of lead are very important. The lead ion detection technologies are introduced here, including spectrophotometry, electrochemical method, atomic absorption spectrometry, and other detection methods, and the methods' applicability, the advantages, and disadvantages are discussed. The detection limits of voltammetry and atomic absorption spectrometry are as low as 0.1 µg/L, and those of atomic absorption spectrometry are as low as 2 µg/L. The detection limit of photometry is higher (0.01 mg/L), but this method can be achieved in most laboratories. The application of different extraction pretreatment technologies in lead ion detection is introduced. The new technologies develop at home and abroad, such as precious metal nanogold technology, paper microfluidic technology, fluorescence molecular probe technology, spectroscopy, and other emerging technologies in recent years, are reviewed, and the principle and application of various technologies are expounded.
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Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.
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Doença Antimembrana Basal Glomerular , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite , Pneumonia em Organização , Pneumonia , Feminino , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Autoanticorpos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicaçõesRESUMO
Background and Objectives: Hip fractures are associated with mortality and poor functional outcomes. The COVID-19 pandemic has affected patterns of care and health outcomes among fracture patients. This study aimed to determine the influence of COVID-19 infection on hip fracture recovery. Materials and Methods: We prospectively collected data on patients with hip fractures who presented at Hualien Tzu Chi Hospital between 9 March 2022 and 9 September 2022. The data included demographic information and functional scores taken before, during, and after surgery. The patients were divided into two groups: COVID-19 (+) and COVID-19 (-). Results: This study recruited 85 patients, 12 of whom (14.12%) were COVID-19 (+). No significant differences in preoperative or perioperative parameters between the two groups were observed. The postoperative Barthel index score was significantly impacted by COVID-19 infection (p = 0.001). The incidence of postoperative complications was significantly correlated with general anesthesia (p = 0.026) and the length of stay (p = 0.004) in hospital. Poor postoperative functional scores were associated with lower preoperative Barthel index scores (p < 0.001). Male sex (p = 0.049), old age (p = 0.012), a high American Society of Anesthesiologists grade (p = 0.029), and a high Charlson comorbidity index score (p = 0.028) were associated with mortality. Conclusions: Hip fracture surgeries were not unduly delayed in our hospital during the COVID-19 pandemic, but the patients' postoperative Barthel index scores were significantly influenced by COVID-19 (+). The preoperative Barthel index score may be a good predictive tool for the postoperative functional recovery of these patients.
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Anthocyanins, naturally found in citrus, play key roles in improving the qualities of citrus fruits and products. Dietary consumption of fruit-derived anthocyanins is concerned increasingly owing to health-promoting properties. However, anthocyanins are vulnerable to many physical and chemical factors during processing and storage, affecting fruit qualities and consumer acceptance. Thus, the aim of this review is to focus on main advances in chemical structures, differential biosynthesis mechanisms, enrichment methods, and bioactivities of anthocyanins in pigmented and unpigmented citrus fruits. In this review, anthocyanin species and concentrations display tissue specificity in citrus, and the chemical structures and contents of main anthocyanins are summarized. For differential biosynthesis mechanisms, the reasons why most citrus fruits lose the ability of anthocyanin biosynthesis compared with pigmented fruits, and the molecular differences of biosynthesis mechanisms in pigmented citrus fruits are both discussed in detail. Furthermore, anthocyanins' enrichment methods (low-temperature stimulus, light irradiation, xenobiotics inductions, and ripeness influence) during processing and storage have been summarized, which achieve quality improvement by promoting structural gene expression, reducing anthocyanin-degrading enzyme activities, or altering DNA methylation status. Meantime, the health benefits of extract from pigmented citrus and their waste are mentioned, which provides a new approach for citrus waste recycling. HIGHLIGHTS⢠Chemical structures of individual anthocyanins in citrus are reviewed.⢠Differential anthocyanin biosynthesis in citrus depends on mutations of Ruby genes.⢠Anthocyanins are enriched in response to exogenous stimulus during storage.⢠Health benefits of extract in blood oranges and their waste are summarized.
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BACKGROUND: The clinicopathological characteristics of solid pseudopapillary tumor (SPT) and pancreatic neuroendocrine neoplasm (pNEN) are different. We, therefore, systematically investigated the performance of the clinicopathological characteristics in distinguishing SPT from pNEN. METHODS: We collected the cases from the Surveillance, Epidemiology, and End Results Program. The International Classification of Diseases for Oncology, third edition (ICD-O-3) for tumors was used to identify patients with pNEN or patients with SPT. To determine the performance of age in combination with gender in distinguishing SPT from pNEN, a nomogram was developed and the performance of this nomogram was evaluated by the receiver operating characteristic curve and the area under the curve (AUC). RESULTS: In the training cohort, 563 patients with pNENs and 30 patients with SPTs were recruited. The logistic regression and receiver operating characteristic curves suggest that age, gender, T-stage, N-stage, and M-stage could discriminate SPT and pNEN. The AUC of age, gender, T-stage, N-stage, and M-stage was 0.82, 0.75, 0.65, 0.69, and 0.70, respectively. Based on the nomogram, we observed that the AUC of age and gender is significantly high than that of the T-stage, N-stage, and M-stage. CONCLUSIONS: The present study proposes a non-invasive nomogram that could aid in the differential diagnosis of pNEN and SPT. This might help the clinicians to distinguish SPT from pNEN and choose the appropriate treatments for the patients.
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Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Diagnóstico Diferencial , Curva ROCRESUMO
TPN729, a novel phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), is in phase II clinical trials in China. Previous studies suggested that TPN729 possesses promising therapeutic value. In previous non-radiolabeled rat excretion studies, the recovery of TPN729 and its major metabolites accounted for approximately 8.58% of the administration dose in urine and faeces by 48 h post-dose.To solve this problem and further study the metabolism of TPN729 in rats, we used the radio-isotopic tracing technique for the first time. In this study, the mass balance, tissue distribution, and metabolism of TPN729 were evaluated in rats after a single oral dose of 25 mg/kg [14C]TPN729 (150 µCi/kg).At 168 h post-dose, the mean total radioactivity recovery of the dose was 92.13%. Faeces was the major excretion route, accounting for 74.63% of the dose, and urine excretion accounted for 17.50%. After oral administration of [14C]TPN729, radioactivity was widely distributed in all examined tissues, and a higher radioactivity concentration was observed in the stomach, large intestine, lung, liver, small intestine, and eyes. The concentration of drug-related materials were similar in plasma and blood cells. A total of 51 metabolites were identified in rat plasma, urine, faeces, and bile, and the predominant metabolically susceptible position of TPN729 was the pyrrolidine moiety. The main metabolic pathways were N-dealkylation, oxidation, and dehydrogenation.In summary, we solved the previous problem of low drug recovery, elucidated the major excretion pathway, determined the tissue distribution patterns, and investigated the metabolism of TPN729 in rats by using a radioisotopic tracing technique.
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Pirimidinonas , Sulfonamidas , Administração Oral , Animais , Fezes , Masculino , Ratos , Sulfonamidas/metabolismo , Distribuição TecidualRESUMO
Background and Objectives: Distal femoral fracture is a severe injury that makes surgery challenging, particularly comminuted fractures in the supracondylar region. This study aimed to evaluate the outcomes of distal femoral fracture treated with the application of an intramedullary fibular allogenic bone strut in open reduction and internal fixation (ORIF) with precontoured locking plates in patients over 50 years of age. Materials and Methods: The study retrospectively enrolled 202 patients over 50 years of age with traumatic comminuted distal femoral fracture (AO/OTA 33-A3, 33-C2 and 33-C3) treated with ORIF with a locking plate from January 2016 to December 2019. The two groups were divided into patients who received an intramedullary allogenic bone strut and those who did not. Patients were followed for at least 1 year, with their function scores and radiographic data recorded. Results: A total of 124 patients were recruited, comprising 60 men and 64 women with an average age of 62.4 ± 8.5 years. The 36 patients who had received an intramedullary allogenic fibular bone strut reported lower postoperative pain scores at 1 month and lower postoperative Knee Society Scores (KSS) at 3 months than the control group. The application of an intramedullary allogenic fibular bone strut appeared to be significantly correlated with better 3-month postoperative KSS. Conclusions: The ORIF of distal femoral comminuted fracture with an intramedullary allogenic fibular bone strut can reduce pain and improve knee function in the early stages of postoperative rehabilitation and may reduce the time to union in patients over 50 years of age.