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Osteomyelitis with high mortality and disability rates is a common clinical disease caused by a bacterial infection that is difficult to cure. Considering the stubborn nature and depth of tissue infection, rapid and effective treatments for osteomyelitis remain an enormous challenge. Calcium hydride (CaH2), as efficient hydrogen/alkaline/calcium donors, is employed for combined osteomyelitis therapy. CaH2 reacts with water to sufficiently generate a strong alkali environment with hydroxide anions (OH-) to inhibit bacterial proliferation and induce bacterial death. The released calcium ions (Ca2+) induce calcium overload to kill bacteria first and then serves as calcium source to promote new bone formation. Another byproduct, hydrogen enhances the bacterial membrane permeability and scavenges excess reactive oxygen species (ROS). After incubation with bacteria, CaH2 significantly increases the permeability of the bacterial membrane, therefore increasing the entry of OH- and Ca2+ into bacterial cells, thereby leading to significant bacterial death. After being applied to S. aureus-infected mouse tibia osteomyelitis, CaH2 materials efficiently kill bacteria, relieve local inflammation, and promote new bone formation in a short time. Overall, bioactive metal hydride-associated "triple" hydrogen/alkaline/calcium therapy provides a new idea for the treatment of deep-site bacterial infection, which is beneficial for relieving the pressure caused by antibiotic-resistant bacteria.
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Calcio , Hidrógeno , Osteomielitis , Osteomielitis/tratamiento farmacológico , Animales , Hidrógeno/química , Calcio/metabolismo , Calcio/química , Ratones , Hidróxido de Calcio/química , Staphylococcus aureus/efectos de los fármacosRESUMEN
Lead-free metal halides are considered as alternatives to lead-based perovskites due to their low toxicity, rich structural diversity, and high luminescence properties. We report millimeter-sized single crystals of a new zero-dimensional (0D) copper(I)-based hybrid material, (AEP)2Cu2Br6·2Br·2H2O (AEP = C6H18N33+), which exhibits bright broadband green photoluminescence (PL) at 510 nm with a Stokes shift of 220 nm and a PL lifetime of 121.1 µs. Density functional theory (DFT) calculations and experimental studies reveal that the green light can be attributed to self-trapping exciton (STE) emission. It is worth mentioning that this crystal has a high photoluminescence quantum yield (PLQY) of 90.5%, which is higher than most copper halides.
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Sonodynamic therapy (SDT), which uses ultrasound to trigger a sonosensitizer to generate reactive oxygen species (ROS), is a promising form of cancer therapy with outstanding tissue penetration depth. However, the sonosensitizer may inevitably spread to surrounding healthy tissue beyond the tumor, resulting in undesired side effects under an ultrasound stimulus. Herein, as glutathione (GSH) is overexpressed in the tumor microenvironment, a GSH-activatable sonosensitizer prodrug was designed by attaching a quencher to tetraphydroxy porphyrin for tumor therapy. The prodrug exhibited poor fluorescence and low ROS generation capacity under ultrasound irradiation but it can be activated by GSH to simultaneously switch on fluorescence emission and ROS generation in tumor site. Compared with the non-quenched sonosensitizer, the designed prodrug exhibited significantly higher tumor/healthy organ fluorescence ratios, due to the specific fluorescence and ROS activation by overexpressed GSH in the tumor. Finally, the prodrug exhibited efficient tumor growth inhibition under ultrasound irradiation, further demonstrating its promise as a GSH-activated sonosensitizer prodrug for highly effective cancer treatment.
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Oxygen-deficient molybdenum oxide (MoOX ) nanomaterials are prepared as novel nanosensitizers and TME-stimulants for ultrasound (US)-enhanced cancer metalloimmunotherapy. After PEGylation, MoOX -PEG exhibits efficient capability for US-triggered reactive oxygen species (ROS) generation and glutathione (GSH) depletion. Under US irradiation, MoOX -PEG generates a massive amount of ROS to induce cancer cell damage and immunogenic cell death (ICD), which can effectively suppress tumor growth. More importantly, MoOX -PEG itself further stimulates the maturation of dendritic cells (DCs) and triggeres the activation of the cGAS-STING pathway to enhance the immunological effect. Due to the robust ICD induced by SDT and efficient DC maturation stimulated by MoOX -PEG, the combination treatment of MoOX -triggered SDT and aCTLA-4 further amplifies antitumor therapy, inhibits cancer metastases, and elicits robust immune responses to effectively defeat abscopal tumors.
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Neoplasias , Óxidos , Humanos , Especies Reactivas de Oxígeno/metabolismo , Molibdeno , Neoplasias/tratamiento farmacológico , Hipoxia , Oxígeno/metabolismo , Línea Celular TumoralRESUMEN
Multiple amplification of tumor oxidative stress has been demonstrated as efficient strategy to enhance the reactive oxygen species (ROS)-mediated cancer therapy. Herein, vanadium-based nanocatalysts, hydrogen vanadium bronzes (HX V2 O5 , for short HVO), were constructed and employed as novel biocatalysts for amplifying tumor oxidative stress and enhancing cancer catalytic therapy. Such HVO nanocatalysts harboring multivalent V element possessed multi-functional catalytic activity in decomposing H2 O2 into â OH and depleting endogenous glutathione (GSH) to dually amplify tumor oxidative stress. Meanwhile, HVO nanocatalysts could also be activated by ultrasound to further triply amplify oxidative stress. The massive intracellular ROS caused mitochondrial dysfunction, DNA damage, cell cycle arrest, and cell proliferation inhibition, further realizing cancer cell death and tumor growth inhibition. Collectively, HVO nanocatalysts highlight the remarkable value of ROS-mediated cancer therapies.
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Neoplasias , Vanadio , Línea Celular Tumoral , Glutatión/metabolismo , Humanos , Hidrógeno , Neoplasias/terapia , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND/AIMS: Increased expression of galectin-1 (Gal-1) in gastric cancer (GC) promotes metastasis and correlates with poor prognosis. The mechanisms by which Gal-1 promotes GC metastasis remain unknown. METHODS: Gal-1and Sphingosine-1-phosphate receptor 1 (S1PR1) were determined by immunohistochemistry(IHC) and quantitative real time polymerase chain reaction (qRT-PCR) in GC specimens. Stably transfected Gal-1 or S1PR1 into SGC7901 and MGC-803 cells, western blot and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. RESULTS: Overexpression of Gal-1 enhanced expression of S1PR1 in SGC-7901 cells, and increased cell invasion, while knockdown Gal-1 in MGC-803 cells reduced S1PR1 expression and diminished invasion. Simultaneous knockdown of Gal-1 and overexpression of S1PR1 in MGC803 cells rescued invasive ability of MGC803 cells. S1PR1 was associated with expression of epithelial-to-mesenchymal transition (EMT) markers in vitro and in clinical samples. EMT induced in MGC-803 cells by TGF-ß1 was accompanied by S1PR1 activation, while knockdown of S1PR1 reduced response to TGF-ß1, suggest that Gal-1 promotes GC invasion by activating EMT through a S1PR1-dependent mechanism. Overexpression of S1PR1 promoted subcutaneous xenograft growth and pulmonary metastases, and enhanced expression of EMT markers. CONCLUSION: Galectin-1 promotes metastasis in gastric cancer through a S1PR1- dependent mechanism, our results indicate that targeting S1PR1 may be a novel strategy to treat GC metastasis.
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Galectina 1/metabolismo , Receptores de Lisoesfingolípidos/metabolismo , Neoplasias Gástricas/patología , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Femenino , Galectina 1/genética , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Metástasis Linfática , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Receptores de Lisoesfingolípidos/antagonistas & inhibidores , Receptores de Lisoesfingolípidos/genética , Receptores de Esfingosina-1-Fosfato , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Tasa de Supervivencia , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
The objective of this study was to analyze the changes of activated partial thromboplastin time (APTT) and D-dimer in severe heatstroke (HS) patients and their value in identifying HS patients and to analyze clinical features and early laboratory test results of heat-related illnesses. Forty-five patients with heat-related illnesses who were admitted to the Department of Emergency and Intensive Care Medicine of Suining Central Hospital from June 2022 to April 2023 were retrospectively analyzed. Patients were divided into 3 groups based on their clinical diagnosis: classic HS group, exertional HS group, and control group. General date and laboratory test results were collected, especially APTT and D-dimer. The receiver operating characteristic curve was used to analyze D-dimer and APTT. : There were differences in gender distribution among the 3 groups. Exertional HS was dominated by male patients, and classic HS was dominated by elderly patients. Binary logistic regression analysis of coagulation index showed a significant correlation between D-dimer and APTT and HS. The receiver operating characteristic curve results showed that APTT and D-dimer had high sensitivity and specificity in the identification of HS with an area under the curve (AUC) of 0.846, sensitivity of 97%, and specificity of 58.3% for APTT and an AUC of 0.861, sensitivity of 72%, and specificity of 91.7% for D-dimer (D-dimerâ +â APTT [AUC, 0.929; sensitivity, 81.8%-91.7%; Pâ <â .001]). : The mortality rate of HS is high, and early diagnosis is particularly important. APTT and D-dimer may be used as markers assisting in identifying HS.
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Biomarcadores , Productos de Degradación de Fibrina-Fibrinógeno , Golpe de Calor , Humanos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Golpe de Calor/sangre , Golpe de Calor/diagnóstico , Golpe de Calor/complicaciones , Masculino , Femenino , Biomarcadores/sangre , Tiempo de Tromboplastina Parcial , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Anciano , Curva ROC , Sensibilidad y EspecificidadRESUMEN
Implant-related osteomyelitis is a formidable hurdle in the clinical setting and is characterized by inflammation, infection, and consequential bone destruction. Therefore, effective reactive oxygen species (ROS) scavenging, bacterial killing, and subsequent bone tissue repair are urgently needed for the treatment of difficult-to-heal osteomyelitis. Herein, we utilized the eddy-thermal effect of magnesium (Mg) implants under an alternating magnetic field (AMF) for the controlled release of H2 gas and ions (OH- and Mg2+) for the treatment of osteomyelitis. H2 released by Mg rods under AMFs effectively scavenged cytotoxic ROS, exhibiting anti-inflammatory effects and consequently disrupting the environment of bacterial infections. In addition, the OH- hindered the energy metabolism of bacteria by effectively neutralizing protons within the microenvironment. Moreover, H2 impaired the permeability of bacterial membranes and expedited the damage induced by OH-. This synergistic AMF-induced H2 and proton depletion treatment approach not only killed both gram-negative and gram-positive bacteria but also effectively treated bacterial infections (abscesses and osteomyelitis). Moreover, Mg2+ released from the Mg rods enhanced and accelerated the process of bone osteogenesis. Overall, our work cleverly exploited the eddy-thermal effect and chemical activity of Mg implants under AMFs, aiming to eliminate the inflammatory environment and combat bacterial infections by the simultaneous release of H2, OH-, and Mg2+, thereby facilitating tissue regeneration. This therapeutic strategy achieved multiple benefits in one, thus presenting a promising avenue for clinical application.
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Conventional bone scaffolds, which are mainly ascribed to highly active osteoclasts and an inflammatory microenvironment with high levels of reactive oxygen species and pro-inflammatory factors, barely satisfy osteoporotic defect repair. Herein, multifunctional self-assembled supramolecular fiber hydrogels (Ce-Aln gel) consisting of alendronate (Aln) and cerium (Ce) ions were constructed for osteoporotic bone defect repair. Based on the reversible interaction and polyvalent cerium ions, the Ce-Aln gel, which was mainly composed of ionic coordination and hydrogen bonds, displayed good injectability and autocatalytic amplification of the antioxidant effect. In vitro studies showed that the Ce-Aln gel effectively maintained the biological function of osteoblasts by regulating redox homeostasis and improved the inflammatory microenvironment to enhance the inhibitory effect on osteoclasts. Ribonucleic acid (RNA) sequencing further revealed significant downregulation of various metabolic pathways, including apoptosis signaling, hypoxia metabolism and tumor necrosis factor-alpha (TNF-α) signaling via the nuclear factor kappa-B pathway after treatment with the Ce-Aln gel. In vivo experiments showed that the clinical drug-based Ce-Aln gel effectively promoted the tissue repair of osteoporotic bone defects by improving inflammation and inhibiting osteoclast formation at the defect. Notably, in vivo systemic osteoporosis was significantly ameliorated, highlighting the strong potential of clinical translation for precise therapy of bone defects.
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Oxidative stress, due to the disruption of the balance between reactive oxygen species (ROS) generation and the antioxidant defense system, plays an important role in the pathogenesis of rheumatoid arthritis (RA). Excessive ROS leads to the loss of biological molecules and cellular functions, release of many inflammatory mediators, stimulate the polarization of macrophages, and aggravate the inflammatory response, thus promoting osteoclasts and bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin natural coordination nanoparticles (Fe-Qur NCNs) with excellent anti-inflammatory and antioxidant properties were constructed to effectively treat RA. Fe-Qur NCNs obtained by simple mixing retain the inherent ability to remove ROS of quercetin and have a better water-solubility and biocompatibility. In vitro experiments showed that Fe-Qur NCNs could effectively remove excess ROS, avoid cell apoptosis, and inhibit the polarization of inflammatory macrophages by reducing the activation of the nuclear factor-κ-gene binding (NF-κB) pathways. In vivo experiments showed that the swollen joints of mice with rheumatoid arthritis treated with Fe-Qur NCNs significantly improved, with Fe-Qur NCNs largely reducing inflammatory cell infiltration, increasing anti-inflammatory macrophage phenotypes, and thus inhibiting osteoclasts, which led to bone erosion. This study demonstrated that the new metal-natural coordination nanoparticles could be an effective therapeutic agent for the prevention of RA and other diseases associated with oxidative stress.
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Osteosarcoma (OS) patients have a poor prognosis due to its high degree of heterogeneity and high rate of metastasis. Magnetic hyperthermia therapy (MHT) combined with immunotherapy is an effective strategy to treat solid and metastatic tumors. Here, we combined biodegradable magnesium (Mg) macroscale rods, which acted as an eddy thermo-magnetic agent under a low external alternating magnetic field, and immunotherapy to achieve a radical cure for OS. The eddy thermal effect (ETE) of the Mg rods (MgR) showed outstanding cytotoxic effects and enhanced the maturation of dendritic cells (DCs), and the mild MHT induced the immunogenic cell death (ICD) in the OS cells. Combined with immune checkpoint blockade (ICB) therapy, we obtained an excellent curative effect against OS, and a further evaluation demonstrated that the local MHT induced by the MgR increased T cells infiltration and the polarization of M1 macrophages. Interestingly, the biodegradable MgR also promoted bone osteogenesis. Our work highlighted the uneven ETE mediated by the biodegradable MgR induced a comprehensive immunologic activation in the OS tumor microenvironment (TME), which would inspire the application of MHT for the effective treatment of OS.
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The further bioapplications of sonodynamic therapy (SDT) were hindered by the inadequate efficiency and poor degradability of sonosensitizers and the hypoxic tumor microenvironment (TME). Therefore, it is ideal to develop pH-sensitive sonosensitizers that generate abundant reactive oxygen species (ROS) and rapidly degrade in a neutral environment while slowly degrading in an acidic environment to reduce their long-term toxicity. Herein, the defective tungsten oxide nanobelts (WOx NBs) were developed as a type of pH-sensitive and biodegradable sonosensitizers with a high SDT efficiency and low toxicity for enhanced SDT. The defective oxygen sites of WOx NBs could inhibit the recombination of electrons and holes, making WOx NBs promising sonosensitizers that could generate abundant ROS under ultrasound (US) irradiation. Enhanced by the catalase (CAT) that reacted with H2O2 to generate O2, the WOx NBs exhibited better SDT performance against 4T1 cells in both normoxic and hypoxic environments. In addition, the WOx NBs could degrade by releasing protons (H+), resulting in intracellular acidification and inhibited cell motility that further enhanced the therapeutic effects of SDT. Assisted with CAT and ALG for hypoxia refinement and better retention, the WOx NBs enabled effective SDT and antimetastasis against 4T1 tumors in vivo. Most importantly, the WOx NBs could degrade rapidly in normal tissues but slowly in an acidic TME, which was favorable for their fast clearance, without any obvious long-term toxicity. Our work developed defective WOx NBs with a high SDT efficiency and pH-sensitive degradation for enhanced SDT, which extended the biomedical application of tungsten-based nanomaterials and the further development of SDT.
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Neoplasias , Terapia por Ultrasonido , Humanos , Tungsteno , Especies Reactivas de Oxígeno/metabolismo , Catalasa , Oxígeno , Protones , Peróxido de Hidrógeno , Neoplasias/terapia , Neoplasias/patología , Concentración de Iones de Hidrógeno , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Oxidative stress and mitochondrial damage are the main mechanisms of ischemia-reperfusion injury in ischemic stroke. Herein, cerium oxide nanoparticles with powerful free radical scavenging ability were used as carriers to load dl-3-n-butylphthalide (NBP-CeO2 NPs) for the combined treatment of ischemic stroke. NBP-CeO2 NPs could eliminate reactive oxygen species (ROS) in mouse brain microvascular endothelial cells and hippocampal neurons after oxygen-glucose deprivation/reoxygenation (OGD/R), and also save mitochondrial membrane potential, morphology, and function, thus alleviating the in vitro blood brain barrier (BBB) disruption and neuronal apoptosis. In the middle cerebral artery embolization/recanalization (MCAO/R) mouse model, the NBP-CeO2 NPs also possessed superior ROS scavenging ability, protected mitochondria, and preserved BBB integrity, thereby reducing cerebral infarction and cerebral edema and inhibiting neuroinflammation and neuronal apoptosis. The long-term neurobehavioral tests indicated that the NBP-CeO2 NPs significantly improved sensorimotor function and spatial learning ability by promoting angiogenesis after ischemic stroke. Therefore, the NBP-CeO2 NPs provided a novel therapeutic approach for ischemic stroke by combining antioxidant and neurovascular repair abilities, highlighting its wide application in ischemia-reperfusion injury.
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Accidente Cerebrovascular Isquémico , Nanopartículas , Daño por Reperfusión , Animales , Ratones , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Especies Reactivas de Oxígeno , Células Endoteliales , Daño por Reperfusión/tratamiento farmacológicoRESUMEN
As safety has been attracting the attention of all countries worldwide, the importance of safety professionals in safety management systems has been emphasized, which has consistently increased their workload. However, with the increase in work pressure, the income, social status, and social identity of safety professionals has not considerably improved, because of which the work motivation of safety professionals has reduced. Therefore, we aimed to identify the job burnout level (JBL) and its potential influencing factors among safety professionals in China. A total of 526 safety professionals from various industries participated. A univariate analysis of variance, independent sample t-test, bivariate correlation analysis, and multiple regression analysis were employed to analyze the situation of job burnout. An overwhelming majority of the safety professionals (98.3%) who participated in the questionnaire exhibited varying degrees of job burnout. The numbers of respondents with higher than normal emotional exhaustion (EE), lack of personal accomplishment (LPA), and depersonalization (DP) levels were 68, 474, and 381, respectively, accounting for 12.9%, 90.1%, and 72.4% of the total respondents, respectively. When different demographic characteristics were reviewed, the job burnout levels considerably varied. For example, male safety professionals (n = 434) exhibited higher levels of EE than female safety professionals (n = 92) (p = 0.025) because female safety professionals could release the dissatisfaction or stress they had encountered at work easily, but male safety professionals could not. Educational background had little effect on LPA (p > 0.05) and EE (p > 0.05), which indicated that job burnout was a general problem at all educational levels. The higher the age of respondents, the higher the level of LPA (p < 0.001). In addition to individual factors, work-related factors also had an impact on job burnout. For instance, monthly income had an impact on EE (p = 0.023) but had little impact on DP (p > 0.05). Furthermore, social, organizational, professional, and personal factors also had an impact on job burnout among safety professionals. Hence, to begin with, these aspects could be considered to alleviate the work pressure of safety professionals and reduce their job burnout levels.
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Agotamiento Profesional , Satisfacción en el Trabajo , Agotamiento Profesional/epidemiología , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Encuestas y Cuestionarios , Carga de TrabajoRESUMEN
Bacterial fruit blotch, caused by seed-borne pathogen Acidovorax citrulli, poses a serious threat to the production of cucurbits globally. Although the disease can cause substantial economic losses, limited information is available about the molecular mechanisms of virulence. This study identified that, a random transposon insertion mutant impaired in the ability to elicit a hypersensitive response on tobacco. The disrupted gene in this mutant was determined to be Aave_0638, which is predicted to encode a YggS family pyridoxal phosphate-dependent enzyme. YggS is a highly conserved protein among multiple organisms, and is responsible for maintaining the homeostasis of pyridoxal 5'-phosphate and amino acids in cells. yggS deletion mutant of A. citrulli strain XjL12 displayed attenuated virulence, delayed hypersensitive response, less tolerance to H2O2 and pyridoxine, increased sensitivity to antibiotic ß-chloro-D-alanine, and reduced swimming. In addition, RNA-Seq analysis demonstrated that yggS was involved in regulating the expression of certain pathogenicity-associated genes related to secretion, motility, quorum sensing and oxidative stress response. Importantly, YggS significantly affected type III secretion system and its effectors in vitro. Collectively, our results suggest that YggS is indispensable for A.citrulli virulence and expands the role of YggS in the biological processes.
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Laparoscopic radical resection is standard treatment for resectable rectal cancer. However, whether high or low inferior mesenteric artery (IMA) ligation should be performed remains controversial. This retrospective cohort study compared the advantages and disadvantages of low vs high IMA ligation in patients undergoing laparoscopic total mesorectal excision for rectal cancer.Rectal cancer patients (nâ=â322) undergoing total mesorectal excision at our institution in 2010 to 17 were enrolled; 174 underwent high IMA ligation group and 148 low IMA ligation (LIMAL group). Baseline data on patients, operative indices, economic indices, pathology findings, perioperative complications, and survival in the 2 groups were analyzed retrospectively.The low IMA ligation group had significantly higher anus retention ratio (Pâ=â.022), shorter hospital stay (Pâ=â.025), lower medical expenses (Pâ=â.032), fewer cases of anastomotic leakage (Pâ=â.023) and anastomotic stricture (Pâ<â.001), and lower incidence of postoperative genitourinary dysfunction (Pâ=â.003). Cox regression analysis indicated that local recurrence, distant metastasis, tumor differentiation, and tumor-node-metastasis stage were independently associated with survival.Low ligation of the IMA during laparoscopic radical resection of rectal cancer appears to be associated with a lower risks for anastomotic leakage, anastomotic stricture, and genitourinary dysfunction, a shorter hospital stay, and lower costs. In contrast, the rate of lymph node harvest, tumor recurrence rate, metastasis, or mortality was not found to be related with the level of IMA ligation.
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Ligadura/métodos , Arteria Mesentérica Inferior/cirugía , Neoplasias del Recto/cirugía , Anciano , Quimioterapia Adyuvante , Femenino , Gastos en Salud , Humanos , Laparoscopía , Tiempo de Internación , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Radioterapia Adyuvante , Neoplasias del Recto/terapia , Análisis de Regresión , Estudios RetrospectivosRESUMEN
BACKGROUND: Galectin-1 (GAL-1), which is encoded by LGALS1, promotes vasculogenic mimicry (VM) in gastric cancer (GC) tissue. However, the underlying mechanism remains unclear. METHODS: Immunohistochemical (IHC) and CD34-periodic acid-Schiff (PAS) double staining were used to investigate Glioma-associated oncogene-1(GLI1) expression and VM in paraffin-embedded sections from 127 patients with GC of all tumor stages. LGALS1 or GLI1 were stably transduced into MGC-803 cells and AGS cells, and western blotting, IHC, CD34-PAS double staining and three-dimensional culture in vitro, and tumorigenicity in vivo were used to explore the mechanisms of GAL-1/ GLI1 promotion of VM formation in GC tissues. RESULTS: A significant association between GAL-1 and GLI1 expression was identified by IHC staining, as well as a significant association between GLI1 expression and VM formation. Furthermore, overexpression of LGALS1 enhanced expression of GLI1 in MGC-803 and AGS cells. GLI1 promoted VM formation both in vitro and in vivo. The effects of GLI1 on VM formation were independent of LGALS1. Importantly, the expression of VM-related molecules, such as MMP2, MMP14 and laminin5γ2, was also affected upon GLI1 overexpression or silencing in GC cell lines. CONCLUSION: GAL-1 promotes VM in GC through the Hh/GLI pathway, which has potential as a novel therapeutic target for treatment of VM in GC.
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Adenocarcinoma/metabolismo , Galectina 1/metabolismo , Proteínas Hedgehog/metabolismo , Imitación Molecular , Neovascularización Patológica , Neoplasias Gástricas/metabolismo , Proteína con Dedos de Zinc GLI1/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patología , Animales , Línea Celular Tumoral , Galectina 1/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones Desnudos , Transducción de Señal , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Proteína con Dedos de Zinc GLI1/genéticaRESUMEN
Although the electronic cross-matching of blood has been widely applied in some developed countries and regions, concern over the risk of undetected red blood cell (RBC) antibodies has limited its application in mainland China.This study was performed to explore the missed detection rate of RBC antibodies in a Chinese population from 2011 to 2016. If the results of 2 consecutive tests of ABO/RhD blood group identification were consistent and antibody screening results were negative, electronic cross-matching of the blood was performed. In addition, traditional serological cross-matching of blood (polybrene method) and a parallel experiment for electronic cross-matching of blood were performed to analyze the missed detection of unexpected RBC antibodies in blood donors and recipients.Using the polybrene method, 40,228 blood samples were tested by parallel traditional serological cross-matching of blood; among these samples, blood compatibility was found in 40,222 cases, primary incompatibility (incompatibility of the donor's erythrocytes with the recipient's serum) was found in 6 cases, and no secondary incompatibility was found. Identification of antibody specificity was performed using panel cells, and all unexpected RBC antibodies were confirmed as anti-Mur alloantibodies in the MNS system.Further improvements in the erythrocyte antigenic spectrum, especially the Mur antigen in Asian populations, are expected to ensure the safety of implementing electronic cross-matching in China.
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Incompatibilidad de Grupos Sanguíneos/epidemiología , Tipificación y Pruebas Cruzadas Sanguíneas/efectos adversos , Isoanticuerpos/análisis , Sistema del Grupo Sanguíneo ABO/inmunología , Donantes de Sangre , Tipificación y Pruebas Cruzadas Sanguíneas/métodos , China/epidemiología , Femenino , Humanos , Estudios Prospectivos , Sistema del Grupo Sanguíneo Rh-Hr/inmunologíaRESUMEN
In this work, a series of isotactic-polypropylene/atactic-polystyrene (iPP/aPS) miktoarm star copolymers, PxSy, was synthesized via an arm-first approach. Varied star macromolecule architectures were fabricated by designing the arm length and the arm numbers (x and y). These miktoarm stars were able to form micelles in selective solvent (N,N'-dimethylformamide (DMF)), in which the insoluble iPP arms formed the core and the soluble aPS arms formed the shell. The miktoarm polymers aggregated to micro-nanoscale binary structures (MNBSes) in the casting process, and their morphologies, including the MNBS shape and size, were greatly influenced by the PxSy architectures. The MNBSes endowed the material surface with superhydrophobic performance with a water contact angle of 157.0° and a sliding angle of 1.5°.
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Several studies suggest that peripheral blood and lymph node micrometastases may be a causative factor for gastric cancer recurrence. Cytokeratin 20 shows enriched expression in intestinal epithelial cells. This study aimed to evaluate the clinical utility of monitoring cytokeratin 20 levels in peripheral blood and lymph nodes of patients with gastric cancer for detecting micrometastasis and predicting prognosis. We detected messenger RNA levels of cytokeratin 20 in gastric cancer cell lines and in the peripheral blood of 125 patients (85 patients with gastric cancer and 40 patients with benign neoplasm) by fluorescence quantitative real-time polymerase chain reaction both before and after radical resection. In all, 1586 lymph node samples from 85 patients with gastric cancer were evaluated for cytokeratin 20 expression using real-time polymerase chain reaction, as well as by immunohistochemistry staining with anti-pan-keratin and anti-cytokeratin 20 antibodies. All patients underwent follow-up until cancer-related death or for more than 3 years after tumor resection. We found that elevated cytokeratin 20 expression in peripheral blood as detected by quantitative real-time polymerase chain reaction closely correlates with poor clinicopathological characteristics. Detecting cytokeratin 20 messenger RNA in the lymph nodes by quantitative real-time polymerase chain reaction enabled more accurate determination of the clinicopathological staging of gastric cancer, best treatment approach, and prognosis. Our findings show that patients with increased cytokeratin 20 messenger RNA expression in the peripheral blood or lymph nodes have a shorter time to recurrence and poorer overall survival.