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BACKGROUND: RAS, BRAF, and mismatch repair (MMR)/microsatellite instability (MSI) are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer (CRC). However, their characteristics and influencing factors in Chinese patients have not been thoroughly described. AIM: To analyze the clinicopathological features of KRAS, NRAS, BRAF, and PIK3CA mutations and the DNA MMR status in CRC. METHODS: We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital. MMR proteins were tested using immunohistochemical analysis, and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction. Microsatellite status was determined using an MSI detection kit. Statistical analyses were conducted using SPSS software and logistic regression. RESULTS: The KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 44.6%, 3.4%, 3.7%, and 3.9% of CRC patients, respectively. KRAS mutations were more likely to occur in patients with moderate-to-high differentiation. BRAF mutations were more likely to occur in patients with right-sided CRC, poorly differentiated, or no perineural invasion. Deficient MMR (dMMR) was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas. KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 29.6%, 1.1%, 8.1%, and 22.3% of patients with dMMR, respectively. The dMMR was more likely to occur in patients with a family history of CRC, aged < 50 years, right-sided CRC, poorly differentiated histology, no perineural invasion, and with carcinoma in situ, stage I, or stage II tumors. CONCLUSION: This study analyzed the molecular profiles of KRAS, NRAS, BRAF, PIK3CA, and MMR/MSI in CRC, identifying key influencing factors, with implications for clinical management of CRC.
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COVID-19 , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Humanos , Beijing/epidemiología , COVID-19/epidemiología , Metagenómica/métodos , Masculino , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Persona de Mediana Edad , Femenino , Gripe Humana/epidemiología , Gripe Humana/virología , Monitoreo Epidemiológico , Adulto , SARS-CoV-2/genética , Anciano , Adolescente , Adulto Joven , Estaciones del Año , Niño , PreescolarRESUMEN
Executive function, including working memory, attention and inhibitory control, is crucial for decision making, thinking and planning. Lisdexamfetamine, the prodrug of d-amphetamine, has been approved for treating attention-deficit hyperactivity disorder and binge eating disorder, but whether it improves executive function under non-disease condition, as well as the underlying pharmacokinetic and neurochemical properties, remains unclear. Here, using trial unique non-matching to location task and five-choice serial reaction time task of rats, we found lisdexamfetamine (p.o) enhanced spatial working memory and sustained attention under various cognitive load conditions, while d-amphetamine (i.p) only improved these cognitive performances under certain high cognitive load condition. Additionally, lisdexamfetamine evoked less impulsivity than d-amphetamine, indicating lower adverse effect on inhibitory control. In vivo pharmacokinetics showed lisdexamfetamine produced a relative stable and lasting release of amphetamine base both in plasma and in brain tissue, whereas d-amphetamine injection elicited rapid increase and dramatical decrease in amphetamine base levels. Microdialysis revealed lisdexamfetamine caused lasting release of dopamine within the medial prefrontal cortex (mPFC), whereas d-amphetamine produced rapid increase followed by decline to dopamine level. Moreover, lisdexamfetamine elicited more obvious efflux of noradrenaline than that of d-amphetamine. The distinct neurochemical profiles may be partly attributed to the different action of two drugs to membranous catecholamine transporters level within mPFC, detecting by Western Blotting. Taken together, due to its certain pharmacokinetic and catecholamine releasing profiles, lisdexamfetamine produced better pharmacological action to improving executive function. Our finding provided valuable evidence on the ideal pharmacokinetic and neurochemical characteristics of amphetamine-type psychostimulants in cognition enhancement.
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Estimulantes del Sistema Nervioso Central , Dimesilato de Lisdexanfetamina , Ratas , Animales , Dimesilato de Lisdexanfetamina/farmacología , Función Ejecutiva , Dopamina , Estimulantes del Sistema Nervioso Central/efectos adversos , Dextroanfetamina/efectos adversos , Dextroanfetamina/farmacocinética , Anfetamina/farmacología , Catecolaminas , CogniciónRESUMEN
Sjögren's syndrome(SS)is a chronic autoimmune disease that affects exocrine glands, especially salivary and lacrimal glands. The main clinical manifestations are dry mouth and dry eyes, but also multi-organ and multi-system can be involved. Cold agglutinin disease(CAD)is an autoimmune disease characterized by red blood cell agglutination in the blood vessels of extremities caused by cold agglutinin at low temperature, resulting in skin microcirculation disturbance, or hemolytic anemia. Cold agglutinin disease is divided into two categories, primary cold agglutinin disease and secondary cold agglutinin disease. Primary cold agglutinin disease is characterized with cold agglutinin titer of 1 â¶4 000 or more and positive Coomb's test. However, the Coomb's test is not necessarily positive and the cold agglutinin titer is between 1 â¶32 and 1 â¶4 000 in secondary cold agglutinin disease. Here, we reported an elderly patient admitted to hospital due to fever. He was diagnosed with respiratory infection, but he showed incompletely response to the anti-infection treatment. Further laboratory tests showed the patient with positive ANA and anti-SSA antibodies. Additionally, the patient complained that he had dry mouth and dry eyes for 1 year. Schirmer test and salivate gland imaging finally confirmed the diagnosis Sjogren's syndrome. During the hospital stay, the blood clots were found in the anticoagulant tubes. Hemolytic anemia was considered as the patient had anemia with elevated reticulocytes and indirect bilirubin. In addition, further examination showed positive cold agglutination test with a titer of 1 â¶1 024, and cold agglutinin disease was an important type of cold-resistant autoimmune hemolytic anemia. Furthermore, the patient developed cyanosis after ice incubating at the tip of the nose. Hence, the patient was diagnosed as CAD and he was successfully treated with glucocorticoids instead of anti-infection treatments. Hence, the patient was diagnosed with SS combined with secondary CAD. SS combined CAD are rarely reported, and they are both autoimmune diseases. The abnormal function of B lymphocytes and the production of autoantibodies might be the common pathogenesis of them. Cold agglutinin disease can lead to severe hemolytic anemia, even life-threatening. In clinical practice, timely recognizing and dealing with CAD might promote the prognosis of the patient.
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Anemia Hemolítica Autoinmune , Anemia Hemolítica , Síndromes de Ojo Seco , Síndrome de Sjögren , Masculino , Humanos , Anciano , Anemia Hemolítica Autoinmune/complicaciones , Anemia Hemolítica Autoinmune/diagnóstico , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Anemia Hemolítica/complicaciones , Síndromes de Ojo Seco/complicaciones , AutoanticuerposRESUMEN
Elephants have long been observed to grip objects with their trunk, but little is known about how they adjust their strategy for different weights. In this study, we challenge a female African elephant at Zoo Atlanta to lift 20-60 kg barbell weights with only its trunk. We measure the trunk's shape and wrinkle geometry from a frozen elephant trunk at the Smithsonian. We observe several strategies employed to accommodate heavier weights, including accelerating less, orienting the trunk vertically, and wrapping the barbell with a greater trunk length. Mathematical models show that increasing barbell weights are associated with constant trunk tensile force and an increasing barbell-wrapping surface area due to the trunk's wrinkles. Our findings may inspire the design of more adaptable soft robotic grippers that can improve grip using surface morphology such as wrinkles.
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Estructuras Animales , Elefantes , Fuerza Muscular , Animales , Femenino , Elefantes/fisiología , Estructuras Animales/fisiologíaRESUMEN
BACKGROUND: Intensive care unit (ICU) nurses are at high risk of burnout and warranting attention. Existing literature found that work frustration was related to burnout, whilst perceived organization support influenced the association of work frustration with burnout. The purpose of this study was to investigate the relationship of work frustration and burnout among ICU nurses, and to examine the moderating effect of perceived organization support in their relationship. METHODS: The cross-sectional study was conducted with a convenience sample of 479 ICU nurses from several 3 tertiary hospitals during December 2021 to May 2022. The Maslach Burnout Inventory-Human services survey (MBI-HSS), National Aeronautics and Space Administration Task Load Index (NASA-TLX) and perceived organization support Scale (POSS) were used to collect data. The PROCESS macro was performed to test the moderation effect of perceived organization support. RESULTS: The total score of burnouts was (55.79 ± 17.20), the total score of work frustration was (7.44 ± 1.86). Burnout was positively correlated with work frustration (r = 0.301, P < 0.001) and negatively correlated with perceived organizational support (r = -0.430, P < 0.001). The moderation model analysis showed that perceived organizational support could moderate the relationship between work frustration and burnout (ß = -0.111, ΔR2 = 0.011, P = 0.007). CONCLUSIONS: The findings highlight the moderating role of perceived organizational support in the relationship between work frustration and burnout. Hence, interventions to reduce burnout among ICU nurses should consider targeting organizational support and work frustration.
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Post-synthesis modification is an effective strategy for the preparation of rare earth organic framework materials and the derivation of high-performance functional materials. Here, we report the preparation of a dual emission Ln-MOF material (Eu-Ca-MOF) using Ca-MOF as the parent framework and introducing Eu3+ ions into its channels through post-synthesis modification. Eu-Ca-MOF has good photoluminescence properties and can be used as a ratiometric fluorescence sensor (I381/I590) to detect Hg2+ ions in water sensitively. The characteristic of Eu-Ca-MOF obtained is that when the material is dispersed in an aqueous solution containing Hg2+ ions, the characteristic emission of the ligand at 381 nm is enhanced, while the characteristic emission of Eu3+ at 590 nm is quenched. The peak-to-height ratio of the two emissions can be used to achieve highly sensitive detection of Hg2+ ions even in the presence of other potentially competing analytes. In addition, Hg2+ induces Eu-Ca-MOF to produce a significant ratiometric luminescence response, which changes its luminescence color from red to blue, which is beneficial to visual analysis of naked eyes. At the same time, Eu-Ca-MOF has a wider detection range (0.02-200 µM), and a lower limit detection (2.6 nM) for Hg2+ ions. The lanthanide compounds prepared by post-synthetic modification provide an effective synthesis strategy for photoluminescent materials.
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Elementos de la Serie de los Lantanoides , Mercurio , Estructuras Metalorgánicas , Iones/análisis , Ligandos , Mercurio/análisis , AguaRESUMEN
D-amphetamine has been used to enhance cognitive performance over the last few decades. Due to the rapid absorption after administration, d-amphetamine shows narrow effective window and severe abuse potential. Lisdexamfetamine, a prodrug of d-amphetamine, reduces the magnitude of plasma d-amphetamine concentration and prolongs the action duration when compared with immediate-release d-amphetamine at equimolar doses. However, the differences of these two drugs, which produce distinct pharmacokinetic characteristics, in cognition improvement still unclear. In present study, we compared the effects of d-amphetamine (i.p) and lisdexamfetamine (p.o) at equimolar doses (0.2, 0.5, 1.5, 4.5, and 13.5 mg/kg of d-amphetamine base) on locomotion, spatial working memory and recognition memory in rats. Given the crucial involvement of dopamine neurotransmitter system within the medial prefrontal cortex (mPFC) in cognitive processing, microdialysis was conducted to profile the difference in neurochemical characteristics between the two drugs. In our results, d-amphetamine ranges from 0.5 to 1.5 mg/kg significantly increased locomotor activity. However, d-amphetamine ranges from 0.2 to 13.5 mg/kg failed to improve spatial working memory and recognition memory in Y-maze-based spontaneous alternation and two-trial delayed alternation tasks of rats, respectively. In contrast, lisdexamfetamine with 4.5 mg/kg significantly increased the locomotion and improved both spatial working and recognition memory. Further, microdialysis showed that lisdexamfetamine induced lower magnitude and longer duration of extracellular dopamine increase than that of d-amphetamine. These results suggest that lisdexamfetamine was more effective than d-amphetamine in improving spatial cognitive performance, which was attributed to the steady and lasting dopamine release pattern within the mPFC.
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Objective: This study is aimed at exploring the association between autophagy and tumor immune infiltration (TII) in colorectal cancer (CRC). Methods and Materials: We downloaded the transcriptome profiling and clinical data for CRC from The Cancer Genome Atlas (TCGA) database and obtained the normal colon transcriptome profiling data from Genotype-Tissue Expression Project (GTEx) database. The list of autophagy-related signatures was obtained from the Human Autophagy Database. We isolated the autophagy-related genes from the CRC gene expression matrix and constructed an autophagy-related prognostic (ARP) risk model. Then, we constructed a multiROC curve to validate the prognostic ability of the ARP risk model. CIBERSORT was used to determine the fractions of 22 immune cells in each CRC sample, and the association between these TII cells and CRC clinical variables was further investigated. Finally, we estimated the association of 3 hub-ARP signatures and 20 different types of TII cell distribution. Results: We classified 447 CRC patients into 224 low-risk and 223 high-risk patients using the median ARP risk score. According to the univariate survival test results, except for gender (P = 0.672), age (P = 0.008), cancer stage, and pathological stage T, M, and N were closely correlated with the prognosis of CRC patients (P < 0.001). Multivariate survival analysis results indicate that age and rescore were the only independent prognostic indicators with significant differences (P < 0.05). After merging the immune cell distribution (by CIBERSORT) with the CRC clinical data, the results indicate that activated macrophage M0 cells exhibited the highest clinical response, which included cancer stage and stage T, N, and M. Additionally, six immune cells were closely associated with cancer stage, including regulatory T cells (Tregs), gamma delta T cells, follicular helper T cells, activated memory CD4 T cells, activated NK cells, and resting dendritic cells. Finally, we evaluated the correlation of ARP signatures with TII cell distribution. Compared with the other correlation, NRG1 and plasma cells (↑), risk score and macrophage M1 (↑), NRG1 and dendritic cell activated (↑), CDKN2A and T cell CD4 memory resting (↓), risk score and T cell CD8 (↑), risk score and T cell CD4 memory resting (↓), and DAPK1 and T cell CD4 memory activated (↓) exhibited a stronger association (P < 0.0001). Conclusions: In summary, we explored the correlation between the risk of autophagy and the TII microenvironment in CRC patients. Furthermore, we integrated different CAR signatures with tumor-infiltrating immune cells and found robust associations between different levels of CAR signature expression and immune cell infiltrating density.
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Neoplasias Colorrectales , Autofagia/genética , Neoplasias Colorrectales/metabolismo , Perfilación de la Expresión Génica , Humanos , Estadificación de Neoplasias , Microambiente Tumoral/genéticaRESUMEN
AIM: To demonstrate the little-known metabolic changes and pathways in patients with colorectal cancer (CRC). METHODS: We used gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) to perform metabolic profiling of urine samples from 163 consecutive patients with CRC and 111 healthy controls without history of gastrointestinal tumors. The metabolic profiles were assayed using multivariate statistical analysis and one-way analysis of variance, and further analyzed to identify potential marker metabolites related to CRC. The GC-TOF/MS-derived models showed clear discriminations in metabolic profiles between the CRC group and healthy control group. RESULTS: We demonstrated that 15 metabolites contributed to the differences. Among them, eleven metabolites were significantly upregulated, while other four metabolites were downregulated in the urine samples of CRC patients compared with healthy controls. Pathway analysis revealed changes in energy metabolism of patients with CRC, which are reflected in the upregulation of glycolysis and amino acid metabolism and the downregulation of lipid metabolism. Our study revealed the metabolic profile of urine from CRC patients and indicated that GC-TOF/MS-based methods can distinguish CRC from healthy controls. CONCLUSION: GC-TOF/MS-based metabolomics has the potential to be developed into a novel, non-invasive, and painless clinical tool for CRC diagnosis, and may contribute to an improved understanding of disease mechanisms.
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Neoplasias Colorrectales , Biomarcadores , Cromatografía de Gases y Espectrometría de Masas , Humanos , Metaboloma , MetabolómicaRESUMEN
Despite having a trunk that weighs over 100 kg, elephants mainly feed on lightweight vegetation. How do elephants manipulate such small items? In this experimental and theoretical investigation, we filmed elephants at Zoo Atlanta showing that they can use suction to grab food, performing a behaviour that was previously thought to be restricted to fishes. We use a mathematical model to show that an elephant's nostril size and lung capacity enables them to grab items using comparable pressures as the human lung. Ultrasonographic imaging of the elephant sucking viscous fluids show that the elephant's nostrils dilate up to [Formula: see text] in radius, which increases the nasal volume by [Formula: see text]. Based on the pressures applied, we estimate that the elephants can inhale at speeds of over 150 m s-1, nearly 30 times the speed of a human sneeze. These high air speeds enable the elephant to vacuum up piles of rutabaga cubes as well as fragile tortilla chips. We hope these findings inspire further work in suction-based manipulation in both animals and robots.
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Elefantes , Animales , SucciónRESUMEN
AIM: We aimed to compare the oncological outcomes of laparoscopy and open resection for patients with rectal cancer following neoadjuvant chemoradiotherapy (NCRT). METHODS: We searched the publications that compared the efficacy of laparoscopic surgery and open thoracotomy in treatment outcomes of rectal cancer after NCRT. All trials analyzed the summary hazard ratios of the endpoints of interest, including survival and individual postoperative complications. RESULTS: Totally, 10 trials met our inclusion criteria. The pooled analysis of 3-year disease-free survival (OR 1.39, 95% CI 0.93-2.06; p = 0.11) and 3-year overall survival (OR 1.01, 95% CI 0.70-1.45; p = 0.97) showed that laparoscopic surgery did not achieve beneficial effects compared with open thoracotomy. The pooled result of duration of surgery indicated that laparoscopic surgery was associated with a trend for longer surgery time (SMD 27.53, 95% CI 1.34-53.72; p = 0.04), shorter hospital stay (SMD -1.64, 95% CI -2.70 to -0.58; p = 0.002), more postoperative complications (OR 0.77, 95% CI 0.60-0.99; p = 0.04), and decreased blood loss (SMD -49.87, 95% CI -80.61 to -19.14; p = 0.001). However, the number of removed lymph nodes, positive circumferential resection margin, as well as complications after surgery showed significant differences between the 2 groups. CONCLUSIONS: We focused on current evidence and reviewed the studies indicating that similar oncological outcomes were associated with laparoscopic surgery following NCRT for patients with locally advanced lower rectal cancer in comparison with open surgery.
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Quimioradioterapia , Laparoscopía , Neoplasias del Recto , Humanos , Terapia Neoadyuvante , Neoplasias del Recto/cirugía , Neoplasias del Recto/terapia , Resultado del TratamientoRESUMEN
CBX8 is the core component of the PCG family protein PRC1 complex. It is overexpressed in many solid tumors and plays an important role in the prognosis and biological behaviors of tumors such as occurrence, development, invasion, and metastasis. However, exploration of the role and molecular mechanism of CBX8 in tumors is still in its infancy. Our study found that the down-regulation of CBX8 expression by RNA interference induced differential expression of several microRNAs in human colon cancer cells. The 5 most differentially expressed miRNA precursors (pre-miRNA) (hsa-miR-363-3p, hsa-miR-378a-3p, hsa-miR-371b-3p, hsa-miR-361-3p, and hsa-miR-576-3p) share a common motif sequence: ARAAAKUGCMC. We selected miR-378a-3p and further revealed that the negative regulation of miRNA expression by CBX8 mainly occurs in the processing of pre-miRNA to mature miRNA. CBX8 uses its own RNA-binding domain to interact with pre-miRNA, and is dependent on its own nuclear localization characteristics to limit nucleoplasmic transport of pre-miRNA. Changing the characteristic sequence of pre-miRNA or mutating the RNA-binding domain and nuclear localization signal of CBX8 can effectively weaken the regulation of miR-378a-3p expression by CBX8. However, our experimental results showed that miR-378a-3p inhibited the malignant expression of human colon cancer cells by targeting PDIA4, resulting in increased activity of caspases-3 and -7. In summary, our study suggests that CBX8 acts as an independent RNA-binding protein to regulate miRNA expression. Simultaneously, this study shows the correlation between the CBX8/miR-378a-3p/PDIA4 pathway and the malignant biological properties of colorectal cancer, suggesting this proposed pathway as a possible therapeutic target for human cancers.
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Neoplasias del Colon/genética , Neoplasias del Colon/patología , Regulación Neoplásica de la Expresión Génica/genética , MicroARNs/genética , MicroARNs/metabolismo , Complejo Represivo Polycomb 1/fisiología , Proteínas de Unión al ARN , Línea Celular Tumoral , Expresión Génica/genética , Humanos , Terapia Molecular Dirigida , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/metabolismo , Proteína Disulfuro Isomerasas/metabolismo , Transducción de Señal/genética , Transducción de Señal/fisiologíaRESUMEN
OBJECTIVE: To examine the effect of Ureaplasma parvum (U. parvum) infection on mouse sperm motility, structure, and fertilizing ability and on embryo development. DESIGN: In vitro model of the effects of U. parvum serovar 3 infection on mouse sperm. SETTING: Basic research laboratory. INTERVENTION(S): None. ANIMALS: Mice. MAIN OUTCOME MEASURE(S): Mouse sperm motility was examined using the swim-up method, and their motility parameters were analyzed using the sperm motility analysis system. Localization and invasion of U. parvum were observed with fluorescence, confocal, and scanning electron microscopy. After in vitro fertilization with U. parvum-infected sperm, the quality of the fertilized egg and embryo development were assessed. RESULT(S): U. parvum was attached and internalized into mouse sperms and localized mainly at the sperm head and midpiece. U. parvum-infected mouse sperms exhibited decreased motility in a dose- and duration-dependent manner. Electron micrographs revealed that U. parvum infection induced the aggregation and morphological destruction of mouse sperm. Infected mouse sperm transported U. parvum into the fertilized egg with reduced fertilization rates, and infected embryo development was impaired. CONCLUSION(S): U. parvum infection caused deterioration of the mouse sperm quality and its functions, which affected the fertilization rate and embryo development.
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Infecciones por Ureaplasma , Ureaplasma , Animales , Desarrollo Embrionario , Fertilización , Masculino , Ratones , Motilidad Espermática , EspermatozoidesRESUMEN
In this systematic review and meta-analysis, 25 clinical trials were systematically reviewed, and meta-analysis was performed with the results of 16 trials. It was found that the risk of surgical site infection was significantly lower in patients who received perioperative immunonutrition than those given standard nutrition. Furthermore, hospital stay was significantly shorter in patients receiving immunonutrition or early enteral nutrition after surgical resection of gastric cancer. Perioperative immunonutrition also significantly reduced white blood cell counts and the level of C-reactive protein in the patients. However, neither CD4+ T cells nor inflammatory cytokines were significantly affected even though immunonutrition was in favor. These findings suggested that patients with gastrointestinal cancer may benefit from perioperative immunonutrition support by reducing surgery-associated complications and shortening hospital stay. The effects and the underlying mechanism of immunonutrition on immunological modulation and inflammatory regulation, however, remain to be further defined.
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Neoplasias Gastrointestinales , Neoplasias Gástricas , Nutrición Enteral , Neoplasias Gastrointestinales/cirugía , Humanos , Tiempo de Internación , Complicaciones Posoperatorias/prevención & control , Neoplasias Gástricas/cirugíaRESUMEN
A dual-optimized adaptive Kalman filtering (DO-AKF) algorithm based on back propagation (BP) neural network and variance compensation was developed for high-sensitivity trace gas detection in laser spectroscopy. The BP neural network was used to optimize the Kalman filter (KF) parameters. Variance compensation was introduced to track the state of the system and to eliminate the variations in the parameters of dynamic systems. The proposed DO-AKF algorithm showed the best performance compared with the traditional multi-signal average, extended KF, unscented KF, KF optimized by BP neural network (BP-KF) and KF optimized by variance compensation (VC-KF). The optimized DO-AKF algorithm was applied to a QCL-based gas sensor system for an exhaled CO analysis. The experimental results revealed a sensitivity enhancement factor of 23. The proposed algorithm can be widely used in the fields of environmental pollutant monitoring, industrial process control, and breath gas diagnosis.
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Radiation-induced lung injury (RILI) is a serious complication in thoracic tumour radiotherapy. It often occurs in clinical chest radiotherapy and acute whole-body irradiation (WBI) caused by nuclear accidents or nuclear weapon attack. Some radioprotective agents have been reported to exert protective effects when given prior to radiation exposure, however, there is no treatment strategy available for preventing RILI. In this study, we demonstrated that heat-killed Salmonella typhimurium (HKST), a co-agonist of Toll-like receptors 2 (TLR2), Toll-like receptors 4 (TLR4) and Toll-like receptors 5 (TLR5), mitigated radiation-induced lung injury through the transforming growth factor-ß (TGF-ß) signalling pathway. We found that HKST alleviated lung hyperaemia and pathological damage after irradiation, indicated that HKST inhibits the early inflammatory reaction of radiation-induced lung injury. Then, for the first time, we observed HKST reduced collagen deposit induced by irradiation in the later phase (7-14 week) of RILI, and we found that HKST inhibited radiation-induced cell apoptosis in lung tissues. We found that HKST reduced the level of TGF-ß and regulated its downstream signalling pathway. Finally, it was found that HKST inhibited radiation-induced epithelial-mesenchymal transition (EMT) in lung tissues. In conclusion, our data showed that HKST effectively mitigated RILI through regulating TGF-ß, provide novel treatment strategy for RILI in whole-body irradiation and radiotherapy.
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Calor , Lesión Pulmonar/prevención & control , Viabilidad Microbiana , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación , Salmonella typhimurium/fisiología , Animales , Femenino , Rayos gamma , Pulmón/microbiología , Pulmón/patología , Pulmón/efectos de la radiación , Lesión Pulmonar/etiología , Lesión Pulmonar/patología , Ratones , Ratones Endogámicos C57BL , Traumatismos Experimentales por Radiación/patologíaRESUMEN
BACKGROUND: Local people in the Himalayan region use a wide range of wild and non-cultivated edible plants (WNEPs) for food, spice, medicinal, and cultural purposes. However, their availability, use, status and contribution to livelihood security are poorly documented, and they have been generally overlooked in recent agro-biodiversity conservation and management programmes. The study aimed to investigate WNEP diversity and current status in a part of the Kailash Sacred Landscape-a transboundary landscape shared by Nepal, India and PR China-in terms of collection, use, management and conservation initiatives. METHODS: Multiple methodologies and tools were used for data collection. A series of participatory tools (45 key informant interviews, 10 focus group discussions, a crop diversity fair, direct observation of species through a transect walk and rapid market assessments) was followed by a household survey (195 respondents) and complemented by a literature review. RESULTS: The study recorded 99 WNEPs belonging to 59 families of which 96 were angiosperms, one gymnosperm and two pteridophytes. Species were used for food, spice, medicine, rituals and income generation. Thirty-five species had multiple uses, including these: 40 species were used for fruit and 31 for vegetables. WNEPs contribute significantly to daily food requirements, especially the vegetables. The use value of Dryopteris cochleata was found highest (0.98) among frequently used vegetable species. The values of informant consensus factor were found maximum for worms in the stomach (0.99) and minimum for skin disease treatment (0.67). Nearly 85% of households depended exclusively on WNEPs for at least more than a month per year. Results on the importance and use of different species, gender roles in WNEP activities and conservation approaches are presented. CONCLUSIONS: People living in the Kailash Sacred Landscape depend significantly on WNEPs, and this is especially critical in times of food shortage. The WNEPs have considerable potential as an important supplement to cultivated food crops. Farmers prioritise species with multiple use values and popular vegetables. However, there are numerous challenges and interventions needed to ensure conservation and management of species and their continued availability to support food security and local livelihoods.
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Plantas Comestibles , Agricultura , Biodiversidad , Conservación de los Recursos Naturales , Productos Agrícolas , Femenino , Abastecimiento de Alimentos , Humanos , MasculinoRESUMEN
The aim of the present study was to investigate the associations between adiponectin receptor 2 (AdipoR2) gene polymorphisms, AdipoR2 protein expression levels and the risk of colorectal cancer (CRC). From April 2012 to May 2015, 281 CRC patients (case group) admitted to the ChinaJapan Friendship Hospital and 325 healthy control subjects (control group) were recruited for the study. Peripheral venous blood samples were collected and the DNA was extracted. Genotyping was performed using denaturing highperformance liquid chromatography in the condition of partial degeneration. Linkage disequilibrium and haplotype were analyzed using SHEsis analysis software. AdipoR2 protein expression levels were detected by immunohistochemistry and logistic regression analysis was performed to determine the risk factors of CRC. The distribution of the TT genotype of AdipoR2 rs10773989 and the CC genotype of AdipoR2 rs1044471 was higher in the case group than in the control group (P<0.05). The AdipoR2 rs10773989 polymorphism was associated with the degree of tumor infiltration in CRC (P<0.05) and the AdipoR2 rs1044471 polymorphism was associated with the degree of differentiation and Dukes' staging in CRC (P<0.05). The CT haplotype was identified as a protective factor, while the TC haplotype was a risk factor in a healthy population. AdipoR2 protein expression was associated with the degree of differentiation, Dukes' staging, degree of tumor infiltration and lymphatic metastasis in CRC (all P<0.05). Logistic regression analysis demonstrated that the TT genotype of AdipoR2 rs10773989 and CC genotype of AdipoR2 rs1044471 were independent risk factors for CRC. The AdipoR2 rs10773989 and rs1044471 polymorphisms may be correlated with the susceptibility to CRC. In addition, the TC haplotype and AdipoR2 positive expression may increase the risk of CRC.
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Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética/métodos , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , RiesgoRESUMEN
Colorectal cancer (CRC) is one of the most common human malignancies and encompasses cancers of the colon and rectum. Although the gold-standard colonoscopy screening method is effective in detecting CRC, this method is invasive and can result in severe complications for patients. The purpose of this study was to determine differences in metabolites between CRC and matched adjacent nontumor tissues from CRC patients, to identify potential biomarkers that may be informative and developed screening methods. Metabolomic analysis was performed on clinically localized CRC tissue and matched adjacent nontumor tissue from 20 CRC patients. Unsupervised analysis, supervised analysis, univariate analysis and pathway analysis were used to identify potential metabolic biomarkers of CRC. The levels of 25 metabolites in CRC tissues were significantly altered compared with the matched adjacent nontumor tissues. Four metabolites (lactic acid, alanine, phosphate and aspartic acid) demonstrated good area under the curve of receiver-operator characteristic with acceptable sensitivities and specificities, indicating their potential as important biomarkers for CRC. Alterations of amino acid metabolism and enhanced glycolysis may be major factors in the development and progression of CRC. Lactic acid, alanine, phosphate, and aspartic acid could be effective diagnostic indicators for CRC.