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Carbon-based CsPbI3 perovskite solar cells without hole transporter (C-PSCs) have achieved intense attention due to its simple device structure and high chemical stability. However, the severe interface energy loss at the CsPbI3/carbon interface, attributed to the lower hole selectivity for inefficient charge separation, greatly limits device performance. Hence, dipole electric field (DEF) is deployed at the above interface to address the above issue by using a pole molecule, 4-trifluoromethyl-Phenylammonium iodide (CF3-PAI), in which the âNH3 group anchors on the perovskite surface and the âCF3 group extends away from it and connects with carbon electrode. The DEF is proven to align with the built-in electric field, that is pointing toward carbon electrode, which well enhances hole selectivity and charge separation at the interface. Besides, CF3-PAI molecules also serve as defect passivator for reducing trap state density, which further suppresses defect-induced non-radiative recombination. Consequently, the CsPbI3 C-PSCs achieve an excellent efficiency of 18.33% with a high VOC of 1.144 V for inorganic C-PSCs without hole transporter.
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Graphene aerogel (GA) has important application potential as piezoresistive sensors due to its low density, high conductivity, high porosity, and good mechanical properties. However, the fabrication of GA-based sensors with good mechanical properties and excellent sensing performance is still challenging. Herein, liquid- metal-modified GAs (GA/LM) are proposed for the development of an excellent GA-based sensor. GA/LM with three-dimensional interconnected layered structure exhibits excellent compressive stress of 41â KPa and fast response time (<20â ms). While generally flexible GA composites cannot be compressed beyond 80 % strain without plastic deformation, GA/LM demonstrates a high compressive strength of 60â kPa under a strain of 90 %. A real-time pressure sensor was fabricated based on GA/LM-2 to monitor swallowing, pulse beating, finger, wrist and knee bending, and even plantar pressure during walking. These excellent features enable potential applications in health detection.
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Liver metastasis is a major cause of mortality for patients with colorectal cancer (CRC). Mismatch repair-proficient (pMMR) CRCs make up about 95% of metastatic CRCs, and are unresponsive to immune checkpoint blockade (ICB) therapy. Here we show that mouse models of orthotopic pMMR CRC liver metastasis accurately recapitulate the inefficacy of ICB therapy in patients, whereas the same pMMR CRC tumors are sensitive to ICB therapy when grown subcutaneously. To reveal local, nonmalignant components that determine CRC sensitivity to treatment, we compared the microenvironments of pMMR CRC cells grown as liver metastases and subcutaneous tumors. We found a paucity of both activated T cells and dendritic cells in ICB-treated orthotopic liver metastases, when compared with their subcutaneous tumor counterparts. Furthermore, treatment with Feline McDonough sarcoma (FMS)-like tyrosine kinase 3 ligand (Flt3L) plus ICB therapy increased dendritic cell infiltration into pMMR CRC liver metastases and improved mouse survival. Lastly, we show that human CRC liver metastases and microsatellite stable (MSS) primary CRC have a similar paucity of T cells and dendritic cells. These studies indicate that orthotopic tumor models, but not subcutaneous models, should be used to guide human clinical trials. Our findings also posit dendritic cells as antitumor components that can increase the efficacy of immunotherapies against pMMR CRC.
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Neoplasias Colorrectales/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Reparación de la Incompatibilidad de ADN , Células Dendríticas , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Interferón gamma/uso terapéutico , Neoplasias Hepáticas Experimentales/inmunología , Neoplasias Hepáticas Experimentales/secundario , Masculino , Ratones Endogámicos C57BLRESUMEN
Electrospinning is a cost-effective and flexible technology for producing nanofibers with large specific surface areas, functionalized surfaces, and stable structures. In recent years, electrospun nanofibers have attracted more and more attention in electrochemical biosensors due to their excellent morphological and structural properties. This review outlines the principle of electrospinning technology. The strategies of producing nanofibers with different diameters, morphologies, and structures are discussed to understand the regulation rules of nanofiber morphology and structure. The application of electrospun nanofibers in electrochemical biosensors is reviewed in detail. In addition, we look towards the future prospects of electrospinning technology and the challenge of scale production.
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Técnicas Biosensibles , Técnicas Electroquímicas , Nanofibras , Técnicas Biosensibles/métodos , Nanofibras/química , Técnicas Electroquímicas/métodos , Nanotecnología/métodos , HumanosRESUMEN
Disease-related biomarkers may serve as indicators of human disease. The clinical diagnosis of diseases may largely benefit from timely and accurate detection of biomarkers, which has been the subject of extensive investigations. Due to the specificity of antibody and antigen recognition, electrochemical immunosensors can accurately detect multiple disease biomarkers, including proteins, antigens, and enzymes. This review deals with the fundamentals and types of electrochemical immunosensors. The electrochemical immunosensors are developed using three different catalysts: redox couples, typical biological enzymes, and nanomimetic enzymes. This review also focuses on the applications of those immunosensors in the detection of cancer, Alzheimer's disease, novel coronavirus pneumonia and other diseases. Finally, the future trends in electrochemical immunosensors are addressed in terms of achieving lower detection limits, improving electrode modification capabilities and developing composite functional materials.
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Técnicas Biosensibles , COVID-19 , Humanos , Inmunoensayo , Técnicas Electroquímicas , COVID-19/diagnóstico , BiomarcadoresRESUMEN
Dietary antioxidants as health promoters for human beings have attracted much attention and triggered tremendous efforts in evaluation of the antioxidant capacity. Unfortunately, no versatile detection system has been designed to date. Due to the possible synergistic effect among antioxidant components in a diversified system, to isolate and quantify an individual antioxidant via a chromatography approach limits the scope for global antioxidant activity assay. Quality inspections with a spectroscopy strategy to any colored food are far from satisfactory. Herein, a photoelectrochemical (PEC) platform with an ultrasensitive titanium dioxide decorated sulfonated graphene (SGE-TiO2) based transducer was introduced for antioxidant monitoring. Under an open circuit potential (zero potential), with extraordinary response, excellent reproducibility and stability, this PEC sensor could be successfully applied for rational analysis of the global antioxidant capacity. Such a highly efficient strategy showed advantages such as simplicity, convenience, high sensitivity and universality, which were also applicable to the detection of colored system. Moreover, the PEC sensor could be employed for practical evaluation of antioxidant capacity of teas. The concerned mechanism was further proposed and adequately discussed. This straightforward yet powerful approach provides a general format for dietary antioxidant assessment in foodstuff industries.
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Antioxidantes/química , Técnicas de Química Analítica/instrumentación , Técnicas Electroquímicas , Grafito/química , Nanotecnología , Azufre/química , Titanio/química , Colorantes Fluorescentes/química , Análisis de los Alimentos/instrumentación , Reproducibilidad de los ResultadosRESUMEN
Angiostrongylus cantonensis can induce central nervous system (CNS) injury and cause human eosinophilic meningitis. The CNS has been found to have high expression of interleukin 33 (IL-33), which promotes the pathogenesis of T-helper 2 (Th2)-related disease. Given the predominantly type 2 response induced by A. cantonensis-infected mice and human, it is likely that IL-33 may play a role in aiding this process. We report here that IL-33 protein and ST2L messenger RNA (mRNA) transcripts in the brains were upregulated during A. cantonensis infection and that both splenocytes and brain mononuclear cells became IL-33 responsive and produced interleukin 5 and interleukin 13. Furthermore, administration of IL-33 to A. cantonensis-infected mice enhanced ST2L expression and cytokine production. Interestingly, brain IL-33 protein and ST2L mRNA levels were elevated 14-21 days after infection in BALB/c mice, compared with C57BL/6 mice. Thus, our data indicate that IL-33 produced in the brain may function as an inflammatory mediator in eosinophilic meningitis induced by A. cantonensis.
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Angiostrongylus cantonensis/inmunología , Angiostrongylus cantonensis/patogenicidad , Sistema Nervioso Central/inmunología , Sistema Nervioso Central/patología , Interleucinas/inmunología , Infecciones por Strongylida/inmunología , Infecciones por Strongylida/patología , Animales , Modelos Animales de Enfermedad , Expresión Génica , Humanos , Interleucina-33 , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Monocitos/inmunología , Receptores de Interleucina-1/biosíntesis , Bazo/inmunología , Células Th2/inmunologíaRESUMEN
BACKGROUND: Ultra-high dose rate (FLASH) radiation has been reported to efficiently suppress tumor growth while sparing normal tissue; however, the mechanism of the differential tissue sparing effect is still not known. Oxygen has long been known to profoundly impact radiobiological responses, and radiolytic oxygen depletion has been considered to be a possible cause or contributor to the FLASH phenomenon. PURPOSE: This work investigates the impact of tissue pO2 profiles, oxygen depletion per unit dose (g), and the oxygen concentration yielding half-maximum radiosensitization (the average of its maximum value and one) (k) in tumor and normal tissue. METHODS: We developed a model that considers the dependent relationship between oxygen depletion and change of radiosensitivity by FLASH irradiation. The model assumed that FLASH irradiation depletes intracellular oxygen more rapidly than it diffuses into the cell from the extracellular environment. Cell survival was calculated based on the linear quadratic-linear model and the radiosensitivity related parameters were adjusted in 1 Gy increments of the administered dose. The model reproduced published experimental data that were obtained with different cell lines and oxygen concentrations, and was used to analyze the impact of parameter uncertainties on the radiobiological responses. This study expands the oxygen depletion analysis of FLASH to normal human tissue and tumor based on clinically determined aggregate and individual patient pO2 profiles. RESULTS: The results show that the pO2 profile is the most essential factor that affects biological response and analyses based on the median pO2 rather than the full pO2 profile can be unreliable and misleading. Additionally, the presence of a small fraction of cells on the threshold of radiobiologic hypoxia substantially alters biological response due to FLASH oxygen depletion. We found that an increment in the k value is generally more protective of tumor than normal tissue due to a higher frequency of lower pO2 values in tumors. Variation in the g value affects the dose at which oxygen depletion impacts response, but does not alter the dose-dependent response trends, if the g value is identical in both tumor and normal tissue. CONCLUSIONS: The therapeutic efficacy of FLASH oxygen depletion is likely patient and tissue-dependent. For breast cancer, FLASH is beneficial in a minority of cases; however, in a subset of well oxygenated tumors, a therapeutic gain may be realized due to induced normal tissue hypoxia.
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Neoplasias , Oxígeno , Humanos , Oxígeno/metabolismo , Tolerancia a Radiación , Neoplasias/radioterapia , Radiobiología , HipoxiaRESUMEN
BACKGROUND: Clonorchiasis has significant socioeconomic importance in endemic areas; however, studies investigating the disease burden in specific sub-regions are lacking. This study aims to address the gap by quantifying the current disease burden caused by clonorchiasis in Guangdong province and assessing its distribution characteristics. METHODS: Comprehensive measures, including prevalence rates, disability-adjusted life years (DALYs), and direct medical costs, were used to assess the disease burden of clonorchiasis. To estimate the prevalence rate, the number of infections was divided by the examined population, based on the annual surveillance data on clonorchiasis cases during 2016-2021. The calculation of DALYs was based on the epidemiological parameters according to the definition issued by the World Health Organization. Cost data of clonorchiasis were utilized to quantify the direct medical costs. The distribution characteristics of disease burden were assessed through comparisons of groups of population defined by geographic area, time, and characteristics of people. RESULTS: In 2021, clonorchiasis posed a significant disease burden in Guangdong Province. The prevalence rate was found to be 4.25% [95% CI (4.02%, 4.49%)], with an associated burden of DALYs of 406,802.29 [95% CI (329,275.33, 49,215,163.78)] person-years. The per-case direct medical costs of patients with clonorchiasis were estimated to be CNY 7907.2 (SD = 5154.4). Notably, while the prevalence rate and DALYs showed a steady decrease from 2016 to 2020, there was a rising trend in 2021. Spatial clustering of clonorchiasis cases and DALYs was also observed, particularly along the Pearl River and Han River. This suggests a concentration of the disease in these regions. Furthermore, significant differences in prevalence rates were found among various demographic groups, including sex, age, occupation, and education level. Additionally, patients with longer hospital stays were more likely to incur higher direct medical costs. CONCLUSIONS: The burden of clonorchiasis in Guangdong Province remains high, despite significant progress achieved through the implementation of the prevention and control programs. It is suggested that measures should be taken based on the distribution characteristics to maximize the effectiveness of prevention and control, with a primary focus on key populations and areas.
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Clonorquiasis , Costo de Enfermedad , Clonorquiasis/epidemiología , Clonorquiasis/parasitología , Humanos , China/epidemiología , Prevalencia , Masculino , Persona de Mediana Edad , Adulto , Femenino , Anciano , Adolescente , Niño , Adulto Joven , Preescolar , Lactante , Años de Vida Ajustados por Discapacidad , Costos de la Atención en Salud/estadística & datos numéricos , Anciano de 80 o más Años , Recién NacidoRESUMEN
Nowadays, two of the biggest obstacles restricting the further development of methanol fuel cells are excessive cost and insufficient catalytic activity of platinum-based catalysts. Herein, platinum nanoparticle supported graphene aerogel (Pt/3DGA) was successfully synthesized by a one-step hydrothermal self-assembly method. The loose three-dimensional structure of the aerogel is stabilized by a simple one-step method, which not only reduces cost compared to the freeze-drying technology, but also optimizes the loading method of nanoparticles. The prepared Pt/3DGA catalyst has a three-dimensional porous structure with a highly cross-linked, large specific surface area, even dispersion of Pt NPs and good electrical conductivity. It is worth noting that its catalytic activity is 438.4 mA/mg with long-term stability, which is consistent with the projected benefits of anodic catalytic systems in methanol fuel cells.. Our study provides an applicable method for synthesizing nano metal particles/graphene-based composites.
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Defects formed at the surface, buried interface and grain boundaries (GB) of CsPbI3 perovskite films considerably limit photovoltaic performance. Such defects could be passivated effectively by the most prevalent post modification strategy without compromising the photoelectric properties of perovskite films, but it is still a great challenge to make this strategy comprehensive to different defects spatially distributed throughout the films. Herein, a spatially selective defect management (SSDM) strategy is developed to roundly passivate various defects at different locations within the perovskite film by a facile one-step treatment procedure using a piperazine-1,4-diium tetrafluoroborate (PZD(BF4)2) solution. The small-size PZD2+ cations could penetrate into the film interior and even make it all the way to the buried interface of CsPbI3 perovskite films, while the BF4- anions, with largely different properties from I- anions, mainly anchor on the film surface. Consequently, virtually all the defects at the surface, buried interface and grain boundaries of CsPbI3 perovskite films are effectively healed, leading to significantly improved film quality, enhanced phase stability, optimized energy level alignment and promoted carrier transport. With these films, the fabricated CsPbI3 PSCs based on carbon electrode (C-PSCs) achieve an efficiency of 18.27%, which is among the highest-reported values for inorganic C-PSCs, and stability of 500 h at 85 °C with 65% efficiency maintenance.
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Angiostrongylus cantonensis is an emerging zoonotic pathogen that has caused hundreds of cases of human angiostrongyliasis worldwide. The larva in nonpermissive hosts cannot develop into an adult worm and can cause eosinophilic meningitis and ocular angiostrongyliasis. The mechanism of brain inflammation caused by the worm remains poorly defined. According to previous data of GeneChip, Ym1 in the brain of mice 21 days after infection with A. cantonensis was highly upregulated to over 7,300 times than the untreated mice. Ym1 is an eosinophilic chemotactic factor with the alternative names of chitinase-3-like protein 3, eosinophil chemotactic cytokine, and ECF-L. Ym1 displays chemotactic activity for T lymphocytes, bone marrow cells, and eosinophils and may favor inflammatory responses induced by parasitic infections and allergy. It has been reported that Ym1 is synthesized and secreted by activated macrophages during parasitic infection (Chang et al., J Biol Chem 276(20):17497-17506, 2001). In the brain, microglia are alternatively activated macrophage-derived cells which are the key immune cells in central nervous system inflammation. To explore the role of Ym1 in inflammation caused by A. cantonensis-infected mice, we examined the levels of Ym1 in the sera and cerebrospinal fluid (CSF) of the infected animals, followed by detection of the mRNA expression level of Ym1 in various organs including the brain, lung, liver, spleen, and kidney and of the cytokines IL-5 and IL-13 in the brain of the infected mice with or without intraperitoneal injection of minocycline (an inhibitor of microglial activation) by real-time reserve transcription PCR. Furthermore, immunolocalization of Ym1 in the brains of the infected mice was observed by using a fluorescence microscope. Our results showed that Ym1 was most highly expressed in the brains and CSF of the infected mice along with the process of inflammation. The antibody localized Ym1 to the microglia in the brain of the mice in both infection and minocycline + infection groups. And as in the brain, the mRNA level of Ym1 changed more obviously than IL-5 and IL-13. The study implies that Ym1 might serve as an alternative potential pathological marker which is detected not only in the sera and CSF but also in the brains of the infected mice and Ym1 secreted by microglia might be involved in eosinophilic meningitis and meningoencephalitis caused by A. cantonensis infection.
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Angiostrongylus cantonensis/inmunología , Angiostrongylus cantonensis/patogenicidad , Encefalitis/inmunología , Encefalitis/patología , Eosinófilos/inmunología , Interacciones Huésped-Patógeno , Lectinas/metabolismo , beta-N-Acetilhexosaminidasas/metabolismo , Estructuras Animales/patología , Animales , Líquido Cefalorraquídeo/química , Modelos Animales de Enfermedad , Encefalitis/parasitología , Femenino , Perfilación de la Expresión Génica , Interleucina-13/genética , Interleucina-5/genética , Lectinas/sangre , Lectinas/líquido cefalorraquídeo , Lectinas/genética , Ratones , Ratones Endogámicos BALB C , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Suero/química , Infecciones por Strongylida/parasitología , Infecciones por Strongylida/patología , beta-N-Acetilhexosaminidasas/sangre , beta-N-Acetilhexosaminidasas/líquido cefalorraquídeo , beta-N-Acetilhexosaminidasas/genéticaRESUMEN
Carbon dots (CDs) are widely used in the detection of foodborne contaminants because of their biocompatibility, photoluminescence stability, and ease of chemical modification. In order to solve the interference problem of complexity in food matrices, the development of ratiometric fluorescence sensors shows great prospects. In this review, the progress of ratiometric fluorescence sensors based on CDs in foodborne contaminant detection in recent years will be summarized, focusing on the functionalized modification of CDs, the fluorescence sensing mechanism, the types of ratiometric fluorescence sensors, and the application of portable devices. In addition, the outlook on the development of the field will be presented, with the development of smartphone applications and related software helping to better enable the on-site detection of foodborne contaminants to ensure food safety and human health.
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Puntos Cuánticos , Humanos , Carbono , Fluorescencia , Inocuidad de los Alimentos , Alimentos , Colorantes FluorescentesRESUMEN
Collagen fibers (CFs) were previously used as packing materials for the separation of flavonoids based on hydrogen bond and hydrophobic interactions. However, as for flavonoid aglycones, CFs presented unsatisfactory adsorption capacity and separation efficiency due to the fact that they include limited hydroxyls and phenyls. In order to improve the adsorption capacity and separation efficiency, the hydrophobic modification strategy was employed in this research to enhance the hydrophobic interaction of CF with flavonoid aglycones by using silane coupling agents with different alkyl chains (isobutyl, octyl, and dodecyl). FT-IR analysis, DSC, TG, SEM, EDS mapping, water contact angle, and absorption time of solvent proved the successful grafting of alkyl chains on the CF without disturbing its special fiber structure, leading to the significantly enhanced hydrophobicity of the CF. The dynamic adsorption and elution behavior of kaempferol and quercetin (the typical flavonoid aglycones) on the hydrophobic CF showed that the adsorption rate and retention rate were largely increased in comparison with the CF without modification. Molecular dynamic simulations indicated that the CF grafted with isobutyls could interact with flavonoid aglycones through the highest synergetic effect of hydrophobic and hydrogen bond interactions, which exhibited the strongest retention to flavonoid aglycones. On further increasing the alkyl length (octyl and dodecyl), the hydrophobic interaction was further enhanced, but the hydrogen bonds were significantly weakened by steric hindrance, which showed that the retention to flavonoid aglycones was appropriately increased but without causing peak tailing. In the column separation of kaempferol and quercetin, the CF with hydrophobic modification presented a greater separation efficiency, with the purity of kaempferol increased from 71.99 to 86.57-97.50% and the purity of quercetin increased from 82.69 to 88.07-99.37%, which was much better than that of polyamide and close to that of sephadex LH 20. Therefore, the hydrophobicity of the CF could be controllably adjusted to enhance the adsorption rate and retention capacity, specifically improving the separation efficiency of flavonoid aglycones.
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Flavonoides , Quercetina , Flavonoides/química , Quempferoles , Adsorción , Espectroscopía Infrarroja por Transformada de Fourier , Interacciones Hidrofóbicas e Hidrofílicas , Colágeno/químicaRESUMEN
In this study, 2-fluoro-5-iodopyridine (2-F-5-IPy) was used as an electrolyte additive, which can not only protect the negative electrode effectively by forming a stable SEI, but also convert dead lithium into active lithium. Benefits from this are a capacity retention of a LiâLiFePO4 cell after 300 cycles from 36.5% to 89.4%, and the symmetrical cell can work stably for more than 800 hours. Therefore, the addition of 2-F-5-IPy can effectively improve the performance of lithium metal batteries.
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BACKGROUND: Liver cirrhosis (LC) is a prevalent and severe disease in China. The burden of LC is changing with widespread vaccination of hepatitis B virus (HBV) and antiviral therapy. However, the recent transition in etiologies and clinical features of LC cases requiring hospitalization is unclear. AIM: To identify the transition in etiologies and clinical characteristics of hospitalized LC patients in Southern China. METHODS: In this retrospective, cross-sectional study we included LC inpatients admitted between January 2001 and December 2020. Medical data indicating etiological diagnosis and LC complications, and demographic, laboratory, and imaging data were collected from our hospital-based dataset. The etiologies of LC were mainly determined according to the discharge diagnosis, and upper gastrointestinal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatocellular carcinoma (HCC), portal vein thrombosis, hepatorenal syndrome, and acute-on-chronic liver failure (ACLF) were considered LC-related complications in our study. Changing trends in the etiologies and clinical characteristics were investigated using logistic regression, and temporal trends in proportions of separated years were investigated using the Cochran-Armitage test. In-hospital prognosis and risk factors associated with in-hospital mortality were also investigated. RESULTS: A total of 33143 patients were included in the study [mean (SD) age, 51.7 (11.9) years], and 82.2% were males. The mean age of the study population increased from 51.0 years in 2001-2010 to 52.0 years in 2011-2020 (P < 0.001), and the proportion of female patients increased from 16.7% in 2001-2010 to 18.2% in 2011-2020 (P = 0.003). LC patients in the decompensated stage at diagnosis decreased from 68.1% in 2001-2010 to 64.6% in 2011-2020 (P < 0.001), and the median score of model for end-stage liver disease also decreased from 14.0 to 11.0 (P < 0.001). HBV remained the major etiology of LC (75.0%) and the dominant cause of viral hepatitis-LC (94.5%) during the study period. However, the proportion of HBV-LC decreased from 82.4% in 2001-2005 to 74.2% in 2016-2020, and the proportion of viral hepatitis-LC decreased from 85.2% in 2001-2005 to 78.1% in 2016-2020 (both P for trend < 0.001). Meanwhile, the proportions of LC caused by alcoholic liver disease, autoimmune hepatitis and mixed etiology increased by 2.5%, 0.8% and 4.5%, respectively (all P for trend < 0.001). In-hospital mortality was stable at 1.0% in 2011-2020, whereas HCC and ACLF manifested the highest increases in prevalence among all LC complications (35.8% to 41.0% and 5.7% to 12.4%, respectively) and were associated with 6-fold and 4-fold increased risks of mortality (odds ratios: 6.03 and 4.22, respectively). CONCLUSION: LC inpatients have experienced changes in age distribution and etiologies of cirrhosis over the last 20 years in Southern China. HCC and ACLF are associated with the highest risk of in-hospital mortality among LC complications.
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BACKGROUND: The role of induction chemotherapy (IC) in oropharyngeal squamous cell carcinoma (OPSCC) remains controversial. Its interpretation can be confounded by heterogeneity in chemosensitivity and human papillomavirus (HPV) status. This study aimed to investigate the prognostic impact of IC response in HPV-positive and -negative OPSCC. METHODS: Patients with OPSCC who underwent IC and concurrent chemoradiotherapy (CCRT) were retrospectively analyzed. Radiologic response to IC by ≥50% was defined as IC-sensitive (IC-s), while lesser response was deemed as IC-resistant (IC-r). Progression-free survival (PFS) and overall survival (OS) were compared between subgroups. RESULTS: A total of 51 HPV-positive and 57 HPV-negative patients were included. IC-s patients accounted for 55.6%, 62.7%, and 49.1% in the entire cohort, HPV-positive, and HPV-negative subgroup, respectively. Compared with IC-r subgroup, IC-s was associated with better clinical outcomes either in the entire cohort (3y-PFS 91.7%vs.43.7%, P < 0.001; 3y-OS 98.3% vs. 67.4%, P = 0.002), the HPV-positive subgroup (3-year PFS 94.7% vs. 47.9%, P < 0.001; 3-year OS 100% vs. 73.5%, P = 0.055) or the HPV-negative subgroup (3-year PFS 88.2% vs. 40.9%, P = 0.001; 3-year OS 96.4% vs. 63.1%, P = 0.026). Multivariate analysis demonstrated that response to IC represents an independent prognosticator for 3-year PFS (HR, 0.088; 95% CI, 0.027-0.289; P < 0.001) and 3-year OS (HR, 0.100; 95% CI, 0.021-0.477; P = 0.004). CONCLUSIONS: Response to IC exerts a critical predictive effect on prognosis of both HPV-positive and -negative OPSCC. Personalized treatment strategy based on IC response is worthy of further exploration in the future.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Humanos , Carcinoma de Células Escamosas/tratamiento farmacológico , Quimioterapia de Inducción , Estudios Retrospectivos , Neoplasias Orofaríngeas/tratamiento farmacológico , Neoplasias Orofaríngeas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello , Pronóstico , Quimioradioterapia , Neoplasias de Cabeza y Cuello/complicacionesRESUMEN
Objective. Irradiation at FLASH dose rates (>40 Gy s-1) has received great attention due to its reported normal tissue sparing effect. The FLASH effect was originally observed in electron irradiations but has since been shown to also occur with both photon and proton beams. Several mechanisms have been proposed to explain the tissue sparing at high dose rates, including effects involving oxygen, such as depletion of oxygen within the irradiated cells. In this study, we investigated the protective role of FLASH proton irradiation on the skin when varying the oxygen concentration.Approach. Our double scattering proton system provided a 1.2 × 1.6 cm2elliptical field at a dose rate of â¼130 Gy s-1. The conventional dose rate was â¼0.4 Gy s-1. The legs of the FVB/N mice were marked with two tattooed dots and fixed in a holder for exposure. To alter the skin oxygen concentration, the mice were breathing pure oxygen or had their legs tied to restrict blood flow. The distance between the two dots was measured to analyze skin contraction over time.Main results. FLASH irradiation mitigated skin contraction by 15% compared to conventional dose rate irradiation. The epidermis thickness and collagen deposition at 75 d following 25 to 30 Gy exposure suggested a long-term protective function in the skin from FLASH irradiation. Providing the mice with oxygen or reducing the skin oxygen concentration removed the dose-rate-dependent difference in response.Significance. FLASH proton irradiation decreased skin contraction, epidermis thickness and collagen deposition compared to standard dose rate irradiations. The observed oxygen-dependence of the FLASH effect is consistent with, but not conclusive of, fast oxygen depletion during the exposure.
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Terapia de Protones , Protones , Ratones , Animales , Terapia de Protones/métodos , Oxígeno , Piel , Fotones , Dosificación RadioterapéuticaRESUMEN
Ultra-high dose rate irradiation has been reported to protect normal tissues more than conventional dose rate irradiation. This tissue sparing has been termed the FLASH effect. We investigated the FLASH effect of proton irradiation on the intestine as well as the hypothesis that lymphocyte depletion is a cause of the FLASH effect. A 16 × 12 mm2 elliptical field with a dose rate of ~120 Gy/s was provided by a 228 MeV proton pencil beam. Partial abdominal irradiation was delivered to C57BL/6j and immunodeficient Rag1-/-/C57 mice. Proliferating crypt cells were counted at 2 days post exposure, and the thickness of the muscularis externa was measured at 280 days following irradiation. FLASH irradiation did not reduce the morbidity or mortality of conventional irradiation in either strain of mice; in fact, a tendency for worse survival in FLASH-irradiated mice was observed. There were no significant differences in lymphocyte numbers between FLASH and conventional-dose-rate mice. A similar number of proliferating crypt cells and a similar thickness of the muscularis externa following FLASH and conventional dose rate irradiation were observed. Partial abdominal FLASH proton irradiation at 120 Gy/s did not spare normal intestinal tissue, and no difference in lymphocyte depletion was observed. This study suggests that the effect of FLASH irradiation may depend on multiple factors, and in some cases dose rates of over 100 Gy/s do not induce a FLASH effect and can even result in worse outcomes.
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Graphene sheets are used for the first time to fabricate a new type of solid-contact ion-selective electrode (SC-ISE) as the intermediate layer between an ionophore-doped solvent polymeric membrane and a glassy carbon electrode. The new transducing layer was characterized by transmission electron microscopy, scanning electron microscopy, cyclic voltammetry and electrochemical impedance spectroscopy. The performance of the new K(+-)selective electrodes was examined by a potentiometric water layer test, potentiometric measurements, and current reversal chronopotentiometry. The obtained potentiometric sensors were characterized with a calibration line of slope close to Nernstian (59.2 mV/decade) within the activity from 10(-4.5) to 0.1 M. The high capacitance of the graphene solid contacts results in a signal that is stable over one week. The short response time is less than 10 s for activities higher than 10(-5) M. The potential drift of the electrodes was calculated from the slope of the curves at longer times (ΔE/Δt = 1.2 × 10(-5) V s(-1) (I = 1 nA) and ΔE/Δt = 5.5 × 10(-5) V s(-1) (I = 5 nA)). All the results indicate that graphene is a promising material for use as a transducer layer for SC-ISEs.