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Determining the evolutionary history of mantle oxygen fugacity (fo2) is crucial, as it controls the fo2 of mantle-derived melts and regulates atmospheric composition through volcanic outgassing. However, the evolution of mantle fo2 remains controversial. Here, we present a comprehensive dataset of plume-derived komatiites, picrites, and ambient mantle-derived (meta)basalts, spanning from ~3.8 Ga to the present, to investigate mantle thermal and redox states evolution. Our results indicate that fo2 of both mantle plume-derived and ambient mantle-derived melts was lower during the Archean compared to the post-Archean period. This increase in the fo2 of mantle-derived melts over time correlates with decreases in mantle potential temperature and melting depth. By normalizing fo2 to a constant reference pressure (potential oxygen fugacity), we show that the fo2 of both the mantle plume and ambient upper mantle has remained constant since the Hadean. These findings suggest that secular mantle cooling reduced melting depth, increasing the fo2 of mantle-derived melts and contributing to atmospheric oxygenation.
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SHORT VEGETATIVE PHASE (SVP), a member of the MADS-box transcription factor family, has been reported to regulate bud dormancy in deciduous perennial plants. Previously, three LcSVPs (LcSVP1, LcSVP2 and LcSVP3) were identified from litchi genome, and LcSVP2 was highly expressed in the terminal buds of litchi during growth cessation or dormancy stages and down-regulated during growth stages. In this study, the role of LcSVP2 in governing litchi bud dormancy was examined. LcSVP2 was highly expressed in the shoots, especially in the terminal buds at growth cessation stage, whereas low expression was showed in roots, female flowers and seeds. LcSVP2 was found to be located in the nucleus and have transcription inhibitory activity. Overexpression of LcSVP2 in Arabidopsis thaliana resulted in a later flowering phenotype compared to the wild-type control. Silencing LcSVP2 in growing litchi terminal buds delayed re-entry of dormancy, resulting in significantly lower dormancy rate. The treatment also significantly up-regulated litchi FLOWERING LOCUS T2 (LcFT2). Further study indicates that LcSVP2 interacts with an AP2-type transcription factor, SMALL ORGAN SIZE1 (LcSMOS1). Silencing LcSMOS1 promoted budbreak and delayed bud dormancy. Abscisic acid (200 mg/L), which enforced bud dormancy, induced a short-term increase in the expression of LcSVP2 and LcSMOS1. Our study reveals that LcSVP2 may play a crucial role, likely together with LcSMOS1, in dormancy onset of the terminal bud and may also serve as a flowering repressor in evergreen perennial litchi.
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Despite modern antiseptic techniques, surgical site infection (SSI) remains a leading complication of surgery. However, the origins of SSI and the high rates of antimicrobial resistance observed in these infections are poorly understood. Using instrumented spine surgery as a model of clean (class I) skin incision, we prospectively sampled preoperative microbiomes and postoperative SSI isolates in a cohort of 204 patients. Combining multiple forms of genomic analysis, we correlated the identity, anatomic distribution, and antimicrobial resistance profiles of SSI pathogens with those of preoperative strains obtained from the patient skin microbiome. We found that 86% of SSIs, comprising a broad range of bacterial species, originated endogenously from preoperative strains, with no evidence of common source infection among a superset of 1610 patients. Most SSI isolates (59%) were resistant to the prophylactic antibiotic administered during surgery, and their resistance phenotypes correlated with the patient's preoperative resistome (P = 0.0002). These findings indicate the need for SSI prevention strategies tailored to the preoperative microbiome and resistome present in individual patients.
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Antiinfecciosos , Infección de la Herida Quirúrgica , Humanos , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/tratamiento farmacológico , Infección de la Herida Quirúrgica/microbiología , Profilaxis Antibiótica , Piel , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
Background and objectives: There are concerns about the serological responses to Coronavirus disease 2019 (COVID-19) vaccines in inflammatory bowel disease (IBD) patients, particularly those receiving anti-TNF therapy. This study aimed to systematically evaluate the efficacy of COVID-19 vaccines in IBD patients receiving anti-TNF therapy. Methods: Electronic databases were searched to identify relevant studies. We calculated pooled seroconversion rate after COVID-19 vaccination and subgroup analysis for vaccine types and different treatments were performed. Additionally, we estimated pooled rate of T cell response, neutralization response, and breakthrough infections in this population. Results: 32 studies were included in the meta-analysis. IBD patients receiving anti-TNF therapy had relatively high overall seroconversion rate after complete vaccination, with no statistical difference in antibody responses associated with different drug treatments. The pooled positivity rate of T cell response was 0.85 in IBD patients receiving anti-TNF therapy. Compared with healthy controls, the positivity of neutralization assays was significantly lower in IBD patients receiving anti-TNF therapy. The pooled rate of breakthrough infections in IBD patients receiving anti-TNF therapy was 0.04. Conclusions: COVID-19 vaccines have shown good efficacy in IBD patients receiving anti-TNF therapy. However, IBD patients receiving anti-TNF have a relatively high rate of breakthrough infections and a low level of neutralization response.
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This study explores the relationship between the storage quality and bacterial microflora in the mushroom Lyophyllum decastes. The surface bacteria of L. decastes were separated by combining the traditional culture plate separation and 16S rRNA sequencing method, to study the effects of ultrasonic (US) treatment on the surface bacteria of L. decastes during storage. The results demonstrated that Pantoea agglomerans and Pseudomonas fluorescens were among the 15 culturable bacteria isolated with traditional plate method during storage, belonging to 2 phyla and 7 genera. US treatment could inhibit the growth and significantly increase cell membrane permeability, and contents extravasation in P. agglomerans, though its inhibitory effect on P. fluorescens was less. The 16S rRNA sequencing revealed, bacteria from 9 phyla and 35 genera were isolated, and P. fluorescens was the dominant species throughout the storage time. These results indicated that the composition of mushroom surface microflora of Control (CK) and US groups are similar, and the bacterial microflora networks analysis also showed a positive correlation. The KEGG annotation for the functional classification of the bacteria showed that a total of 328 pathways were acquired at the KEGG l3 level, and the relative abundance of membrane transport, amino acid metabolism, carbohydrate metabolism, and energy metabolism pathway was high. Moreover, the relative abundance of the surface bacteria of L. decastes also decreased. Hence, the US treatment had a better bacteriostatic effect, maintained the whiteness index and firmness, and improved the sensory quality of L. decastes during storage.
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Agaricales , Ultrasonido , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Agaricales/química , BacteriasRESUMEN
ABSTRACT: Coagulopathy after traumatic brain injury (TBI) is common and has been closely associated with poor clinical outcomes for the affected patients. Traumatic brain injury-induced coagulopathy (TBI-IC) is consumptive in nature and evolves rapidly from an injury-induced hypercoagulable state. Traumatic brain injury-induced coagulopathy defined by laboratory tests is significantly more frequent than clinical coagulopathy, which often manifests as secondary, recurrent, or delayed intracranial or intracerebral hemorrhage. This disparity between laboratory and clinical coagulopathies has hindered progress in understanding the pathogenesis of TBI-IC and developing more accurate and predictive tests for this severe TBI complication. In this review, we discuss laboratory tests used in clinical and research studies to define TBI-IC, with specific emphasis on what the tests detect and what they do not. We also offer perspective on developing more accurate and predictive tests for this severe TBI complication.
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Trastornos de la Coagulación Sanguínea , Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Trombofilia , Humanos , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/complicaciones , Lesiones Encefálicas/complicaciones , Trombofilia/complicacionesRESUMEN
BACKGROUND AND IMPORTANCE: Spinal vascular malformations (sVMs) are relatively uncommon, accounting for 5% to 10% of all spinal cord lesions. Spetzler and Kim developed a paradigm to classify sVMs based on a variety of characteristics into 1 of 6 types, including a subcategory for exclusively epidural sVMs. There is a paucity of literature focused on this category, specifically sources describing the clinical manifestation and management of these lesions. CLINICAL PRESENTATION: We report 2 cases of purely epidural spinal arteriovenous fistula, with an emphasis on the radiographic features and combined endovascular and microsurgical treatment. We report 2 patients known to have epidural spinal arteriovenous fistula who underwent both embolization and surgical resection between May 2019 and August 2020 at our institution. Data collected included demographic, clinical, and operative course, including age, sex, medical history, presenting symptoms, and preoperative and postoperative imaging. Both of these patients were managed with a combination of an endovascular approach for embolization of feeding arterial source and surgical exploration/resection. In both cases, no residual vascular malformation was identified, and the patients went on to be symptom free after 6 weeks. CONCLUSION: This report describes the use of a combination of endovascular and surgical approaches to achieve maximal benefit for 2 patients. These cases reinforce the value of a staged multimodal treatment approach in achieving good functional outcomes for patients with these rare and challenging entities.
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Fístula Arteriovenosa , Malformaciones Arteriovenosas , Embolización Terapéutica , Humanos , Resultado del Tratamiento , Malformaciones Arteriovenosas/diagnóstico por imagen , Malformaciones Arteriovenosas/cirugía , Embolización Terapéutica/métodos , Fístula Arteriovenosa/cirugía , Microcirugia/métodosRESUMEN
Lyophyllum decastes is a common mushroom that is prone to browning during prolonged storage. In this study, the effects of ultrasonic treatment on metabolic gene expression, enzyme activity, and metabolic compounds related to L. decastes browning were investigated. Treatment of the fruiting body at 35 kHz and 300 W for 10 min reduced the browning index of L. decastes by 21.0 % and increased the L* value by 11.1 %. Ultrasonic treatment of the fruiting body resulted in higher levels of total phenols, flavonoids, and 9 kinds of amino acid with catalase (CAT) and peroxidase (POD) activities maintained at high levels. Higher cytochrome c oxidase (CCO), succinate dehydrogenase (SDH), phosphofructokinase (PFK), and pyruvate kinase (PK) activities may be ascribed to increased antioxidant capacity. Moreover, ultrasonication retained higher adenosine triphosphate (ATP) concentrations with an increased energy charge, while there were lower levels of adenosine diphosphate (ADP) and reduced and oxidized nicotinamide adenine dinucleotide (NADH and NAD+), respectively. Meanwhile, lower lignin contents were observed, along with retarded polyphenol oxidase (PPO) and lipoxygenase (LOX) activities. Lower PPO activity reduced the fruiting body enzymatic browning rate through decreased expression of LdPpo1, LdPpo2, and LdPpo3 during storage at 4 °C for 16 days. This activity may be used to determine the effectiveness of ultrasonication.
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NAD , Succinato Deshidrogenasa , Adenosina Difosfato/metabolismo , Adenosina Trifosfato/metabolismo , Agaricales , Aminoácidos/metabolismo , Antioxidantes/metabolismo , Catalasa/metabolismo , Catecol Oxidasa/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Metabolismo Energético , Flavonoides , Lignina/metabolismo , Lipooxigenasas/metabolismo , NAD/metabolismo , Fenoles/química , Fosfofructoquinasas/metabolismo , Piruvato Quinasa/metabolismo , Succinato Deshidrogenasa/metabolismo , UltrasonidoRESUMEN
Ganoderma resinaceum is a valuable Chinese medicine. This study aimed to investigate whether a G. resinaceum alcohol extract (GRAE) improves sleep, and analyze the potential mechanism. After 30 days of continuous administration of GRAE at various doses, GRAE (1,000 mg/kg.bw) prolonged pentobarbital sodium-induced sleep, increased the rate of sleeping in mice treated with a subthreshold dose of pentobarbital sodium, and shortened sleep latency. The mice brain was analyzed using UPLC-MS/MS and RNA-sequencing. Metabolomics analysis revealed that 73 metabolites in the high-dose (HD) group had changed significantly, mainly in amino acids and their derivatives, especially the accumulation of L-glutamine and PGJ2 (11-oxo-15S-hydroxy-prosta-5Z, 9, 13E-trien-1-oic acid). Transcriptome analysis revealed 500 differential genes between HD and control groups, mainly enriched in neuroactive ligand-receptor interaction, amphetamine addiction, and cocaine addiction pathways. The conjoint analysis of the transcriptome and metabolome showed that the biosynthesis of L-glutamine might be regulated by Homer1, Homer3, and Grin3b. This suggests that GRAE may affect L-glutamine accumulation by regulating the expression of these genes. This study showed that GRAE may prolong the sleep time of mice by reducing the accumulation of L-glutamine and deepens our understanding of the regulatory network between certain genes and L-glutamine.
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Ethanolic fermentation is frequently performed under conditions of low nitrogen. In Saccharomyces cerevisiae, nitrogen limitation induces macroautophagy, including the selective removal of mitochondria, also called mitophagy. Previous research showed that blocking mitophagy by deletion of the mitophagy-specific gene ATG32 increased the fermentation performance during the brewing of Ginjo sake. In this study, we tested if a similar strategy could enhance alcoholic fermentation in the context of fuel ethanol production from sugarcane in Brazilian biorefineries. Conditions that mimic the industrial fermentation process indeed induce Atg32-dependent mitophagy in cells of S. cerevisiae PE-2, a strain frequently used in the industry. However, after blocking mitophagy, no significant differences in CO2 production, final ethanol titers, or cell viability were observed after five rounds of ethanol fermentation, cell recycling, and acid treatment, which is commonly performed in sugarcane biorefineries. To test if S. cerevisiae's strain background influenced this outcome, cultivations were carried out in a synthetic medium with strains PE-2, Ethanol Red (industrial), and BY (laboratory) with and without a functional ATG32 gene and under oxic and oxygen restricted conditions. Despite the clear differences in sugar consumption, cell viability, and ethanol titers, among the three strains, we did not observe any significant improvement in fermentation performance related to the blocking of mitophagy. We concluded, with caution, that the results obtained with Ginjo sake yeast were an exception and cannot be extrapolated to other yeast strains and that more research is needed to ascertain the role of autophagic processes during fermentation. IMPORTANCE Bioethanol is the largest (per volume) ever biobased bulk chemical produced globally. The fermentation process is well established, and industries regularly attain nearly 85% of maximum theoretical yields. However, because of the volume of fuel produced, even a small improvement will have huge economic benefits. To this end, besides already implemented process improvements, various free energy conservation strategies have been successfully exploited at least in laboratory strains to increase ethanol yields and decrease byproduct formation. Cellular housekeeping processes have been an almost unexplored territory in strain improvement. It was previously reported that blocking mitophagy by deletion of the mitophagy receptor gene ATG32 in Saccharomyces cerevisiae led to a 2.1% increase in final ethanol titers during Japanese sake fermentation. We found in two commercially used bioethanol strains (PE-2 and Ethanol Red) that ATG32 deficiency does not lead to a significant improvement in cell viability or ethanol levels during fermentation with molasses or in a synthetic complete medium. More research is required to ascertain the role of autophagic processes during fermentation conditions.
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Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Bebidas Alcohólicas , Proteínas Relacionadas con la Autofagia , Etanol , Fermentación , Microbiología Industrial , Mitofagia , Receptores Citoplasmáticos y Nucleares , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genéticaRESUMEN
The combination of hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been confirmed as an important risk biomarker in several cancers. Hence, we aimed at evaluating the prognostic value of the HALP score in patients with non-metastatic upper tract urothelial carcinoma (UTUC). We retrospectively enrolled 533 of the 640 patients from two centers (315 and 325 patients, respectively) who underwent radical nephroureterectomy (RNU) for UTUC in this study. The cutoff value of HALP was determined using the Youden index by performing receiver operating characteristic (ROC) curve analysis. The relationship between postoperative survival outcomes and preoperative HALP level was assessed using Kaplan-Meier analysis and Cox regression analysis. As a result, the cutoff value of HALP was 28.67 and patients were then divided into HALP<28.67 group and HALP≥28.67 group. Kaplan-Meier analysis and log-rank test revealed that HALP was significantly associated with overall survival (OS) (P<0.001) and progression-free survival (PFS) (P<0.001). Multivariate analysis demonstrated that lower HALP score was an independent risk factor for OS (HR=1.54, 95%CI, 1.14-2.01, P=0.006) and PFS (HR=1.44, 95%CI, 1.07-1.93, P=0.020). Nomograms of OS and PFS incorporated with HALP score were more accurate in predicting prognosis than without. In the subgroup analysis, the HALP score could also stratify patients with respect to survival under different pathologic T stages. Therefore, pretreatment HALP score was an independent prognostic factor of OS and PFS in UTUC patients undergoing RNU.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Neoplasias Urológicas , Albúminas , Carcinoma de Células Transicionales/cirugía , Hemoglobinas/análisis , Humanos , Linfocitos , Nefroureterectomía , Pronóstico , Estudios Retrospectivos , Neoplasias Urológicas/cirugíaRESUMEN
Global enhanced human activities have deeply influenced grassland ecosystems. Quantifying the impact of human activities on grasslands is crucial to understanding the grassland dynamic change mechanism, such as grassland degradation, and to establishing ecosystem protection measures. In this study, potential net primary productivity (PNPP), actual NPP (ANPP), and the forage harvest NPP (HNPP) were employed to establish the human activities index (HAI) to reveal the spatiotemporal changes of the effects of human activities on grassland ecosystems in eastern Inner Mongolia from 2000 to 2017, and to further explore the relationship between human activities and grassland degradation. The results showed that the total average PNPP, ANPP, and HNPP of grasslands in eastern Inner Mongolia were 187.2 Tg C yr-1, 152.3 Tg C yr-1, and 8.9 Tg C yr-1, respectively, during the period of 2000 to 2017. The HAI exhibited a clear decreasing trend during the study period, with annual mean values ranging from 0.75 to 0.47, which indicates that the NPP loss induced by human activities is weakening, and this trend is dominated by the difference between potential NPP and actual NPP. About 42.4% of the study area was non-degraded grassland, and the declining grassland degradation index (GDI) indicated that the degradation grade in eastern Inner Mongolia improved from moderate to light degradation. A positive relationship was found between HAI and GDI. This relationship was more significant in Xilingol League, which is a typical ecologically fragile area, than that in Xing'an League and Hulunbuir City.
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Androgen receptor (AR) is an androgen-activated transcription factor of the nuclear receptor superfamily. AR plays a role in the development and progression of prostate cancer (PCa). However, the exact role of AR in PCa metastasis remains unclear. In the present study, we aimed to elucidate the function of AR in PCa. We found that eukaryotic translation initiation factor (EIF) 5A2, an elongation factor that induces epithelial-to-mesenchymal transition (EMT) in PCa cells, was significantly upregulated after 5α-dihydrotestosterone (DHT) stimulation and downregulated after anti-androgen bicalutamide treatment in PCa cells with high AR expression, but not in cells with low AR expression. Moreover, eIF5A2 knockdown could eliminate DHT-induced invasion and migration of AR-positive PCa cells. DHT treatment decreased epithelial expression of E-cadherin and ß-catenin but increased the expression of the mesenchymal marker proteins Vimentin and N-cadherin. DHT therefore induced EMT, and knockdown of eIF5A2 inhibited DHT-induced EMT. Moreover, in vivo study, Luciferase signals from the lungs of the eIF5A2 plasmid group indicated higher metastasis ability, and the eIF5A2 siRNA group had lower metastasis ability. Our results suggest that AR positively regulates eIF5A2 expression in androgen-dependent cells, and stimulation of AR expression and signaling in prostate tumors promotes PCa metastasis by EMT induction and upregulation of eIF5A2.
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Prostate cancer is the most common malignancy among men worldwide. Platinum (II)-based chemotherapy has been used to treat a number of malignancies including prostate cancer. However, the potential of cisplatin for treating prostate cancer is restricted owing to its limited efficacy and toxic side effects. Combination therapies have been proposed to increase the efficacy and reduce the toxic side effects. In the present study, we investigated how isoalantolactone (IATL), a sesquiterpene lactone extracted from the medicinal plant Inula helenium L., acts synergistically with cisplatin on human prostate cancer cells. We show that IATL significantly increased cisplatin-induced growth suppression and apoptosis in human prostate cancer cells. Mechanistically, the combined treatment resulted in an excessive accumulation of intracellular reactive oxygen species (ROS), which leads to the activation of endoplasmic reticulum (ER) stress and the JNK signaling pathway in human prostate cancer cells. Pretreatment of cells with the ROS scavenger N-acetylcysteine (NAC) significantly abrogated the combined treatment-induced ROS accumulation and cell apoptosis. In addition, the activation of ER stress and the JNK signaling pathway prompted by IATL and cisplatin was also reversed by NAC pretreatment. In vivo, we found that IATL combined with cisplatin showed the strongest antitumor effects compared with single agents. These results support the notion that IATL and cisplatin combinational treatment may be more effective for treating prostate cancer than cisplatin alone.
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STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine the rate of recurrent or adjacent-level stenosis requiring reoperation after single-door cervical laminoplasty for spondylotic myelopathy at our institution. SUMMARY OF BACKGROUND DATA: Adjacent-level stenosis requiring reoperation is a commonly evaluated condition for anterior or posterior arthrodesis, however, there are few studies that evaluate adjacent-level stenosis in the case of cervical laminoplasty. METHODS: Retrospective review of adults undergoing cervical laminoplasty for spondylotic myelopathy between January 2005 and May 2018 at our institution. Demographics, symptom duration, stenotic levels, preoperative and postoperative Medical Research Council motor, American Spinal Injury Association, modified Japanese Orthopaedic Association scores, and Nurick grade were obtained. Postoperative data included presence of C5 palsy, infection rate, alleviation or persistence of symptoms, and rate of recurrent or adjacent-level stenosis. RESULTS: A total of 102 patients underwent cervical laminoplasty; mean age was 56.7 years (±12.96). Most were men (n=76, 74.5%), with myelopathy (n=64, 63.4%), C4 (n=94, 93.1%), and C5 (n=92, 91.1%) cervical stenosis; mean symptom duration was 55 days (7 d to 2.8 y). Average follow-up was 6.4 months (±3.4). After surgery, there was statistically significant improvement in Nurick grade (3.1±2.2 vs. 2.7±2.4, P=0.002) and modified Japanese Orthopaedic Association score (11.4±3.7 vs. 13.9±3.6, P<0.001); American Spinal Injury Association scores also improved (P<0.001). Rate of postoperative C5 palsy was 7.8% (n=8); postoperative infection rate was 1.96% (n=2). Reoperation rate was 4.9% (n=5); reoperation for recurrent or adjacent-level stenosis was 1.96% (n=2). CONCLUSIONS: Recurrent or adjacent-level stenosis requiring reoperation after cervical laminoplasty is rare. Longitudinal studies are needed to verify correlation between motion preservation and incidence of adjacent or recurrent stenosis. LEVEL OF EVIDENCE: Level III-treatment benefits: nonrandomized controlled cohort/follow-up study.
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Laminoplastia , Enfermedades de la Médula Espinal , Adulto , Vértebras Cervicales/cirugía , Estudios de Seguimiento , Humanos , Laminectomía , Laminoplastia/efectos adversos , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Enfermedades de la Médula Espinal/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: The prolapse of a ruptured and extruded bladder after vaginal hysterectomy is rare in clinical practice. We report the case of a significant mass that prolapsed from the vagina after a vaginal hysterectomy in a multiparous postmenopausal woman. CASE PRESENTATION: A 67-year old multiparous postmenopausal Chinese woman was found to have a significant mass extruding from the vagina after a vaginal hysterectomy. The mass was a ruptured and everted bladder, and the diagnosis was confirmed after physical and imaging examinations and urethral catheterization. The patient underwent an emergency operation for mass reduction, bladder repair, and partial colpocleisis under general anesthesia. She recovered without prolapse or urinary drainage complications after 35 months of follow-up. CONCLUSIONS: The present case serves as a guide for the management of patients with pelvic organ prolapse. The condition of patients should be carefully evaluated before surgery, and individualized operation should be performed. Careful postoperative follow-up is crucial for the timely exclusion of complications, especially in elderly patients with persistently increased abdominal pressure.
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Cistostomía , Histerectomía Vaginal/efectos adversos , Prolapso de Órgano Pélvico/cirugía , Vejiga Urinaria/cirugía , Incontinencia Urinaria/etiología , Anciano , Femenino , Humanos , Posmenopausia , Resultado del Tratamiento , Vejiga Urinaria/diagnóstico por imagen , Cateterismo Urinario , Procedimientos Quirúrgicos Urológicos , Vagina/cirugíaRESUMEN
Glucose levels and type 2 diabetes (T2D) are both associated with tumorigenesis and epithelial-mesenchymal transitions (EMTs). EMTs facilitate bladder cancer (BC) metastasis development, but the mechanism by which high-glucose levels promote these EMTs in BC remains unclear. Therefore, we sought to elucidate the mechanism underlying EMT promotion due to increased glucose levels. T24 and UMUC-3 cells were cultured in media containing different glucose concentrations. YAP1, TAZ, GLUT1 and EMT-associated marker expression was analysed via Western blotting and qPCR. BC cell proliferation and invasion were assessed using MTT and Transwell assays, respectively. A xenograft nude mouse model of diabetes was used to evaluate tumour growth and metastasis in vivo. T2D was positively associated with pathologic grade (P = .016) and TNM stage (P < .001) in BC. High glucose triggered BC cell proliferation and invasion in both in vitro and in vivo conditions. High-glucose levels also promoted EMTs in BC cells and increased YAP1 and TAZ expression. YAP1 or TAZ knockdown altered EMT marker expression and decreased GLUT1 expression. Overall, our results suggest that high-glucose levels promote EMTs in BC cells via YAP1 and TAZ regulation. These effector molecules may be promising therapeutic targets for BC cases comorbid with T2D.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Glucosa/toxicidad , Transactivadores/metabolismo , Factores de Transcripción/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Medios de Cultivo , Femenino , Transportador de Glucosa de Tipo 1/metabolismo , Humanos , Hiperglucemia/complicaciones , Masculino , Metformina/farmacología , Ratones Desnudos , Persona de Mediana Edad , Modelos Biológicos , Invasividad Neoplásica , Metástasis de la Neoplasia , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas Señalizadoras YAPRESUMEN
Sustained activation of PI3K-Akt-mTOR cascade is important for renal cell carcinoma (RCC) cell progression. GNE-477 is a novel and efficacious PI3K-mTOR dual inhibitor. The current study tested its anti-RCC cell activity. In the primary cultured human RCC cells, GNE-477 potently inhibited cell growth, viability and proliferation, as well as cell cycle progression, migration and invasion. Furthermore, it induced robust apoptosis activation in primary RCC cells, but being non-cytotoxic to HK-2 epithelial cells and primary human renal epithelial cells. In the primary RCC cells GNE-477 inactivated PI3K-Akt-mTOR cascade by blocking phosphorylation of p85, Akt1, p70S6K1 and S6. Restoring Akt-mTOR activation by a constitutively-active Akt1 reversed GNE-477-induced anti-RCC cell activity. In nude mice intraperitoneal injection of GNE-477 potently suppressed RCC xenograft tumor growth. Collectively, targeting PI3K-Akt-mTOR cascade by GNE-477 inhibits RCC cell growth in vitro and in vivo.
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Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacología , Transducción de Señal/efectos de los fármacos , Tiofenos/farmacología , Animales , Apoptosis/efectos de los fármacos , Carcinoma de Células Renales/metabolismo , Técnicas de Cultivo de Célula , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Neoplasias Renales/metabolismo , Ratones , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
EDITOR'S NOTE: EDITOR'S NOTE In 2019, the clinical practice guideline of integrated traditional Chinese and western medicine atlantoaxial dislocation (ADD) was developed by the professional committee of spine medicine of the Chinese Association for Integration of Chinese and Western medicine, aiming at the major clinical problems of atlantoaxial dislocation (AAD) endangering the life center of the medulla oblongata in the field of spine surgery. More than 40 experts at home and abroad in the field of cervical spine surgery organized the first guide for the diagnosis and treatment of AAD. Guided by the principles of evidence based medicine and the consensus of experts, this guideline is based on the theory of "combination of disease and syndrome, from supervision to treatment" for the diagnosis and treatment of AADï¼based on the treatment principles of "spinal cord decompression, reconstruction of atlantoaxial stability"ï¼based on Tan technology, Goel technology, Abumi technology and other core technologies for surgical treatment. The main content includes four partsï¼AAD diagnosis standard, TCM syndrome differentiation, clinical classification, treatment strategy and method. It provides academic guidance to solve the clinical situation of AAD, which is "unclear definition of diagnosis and classification, confused choice of treatment strategy". ABSTRACT: Clinical Practice Guideline of Integrated Traditional Chinese and Western Medicineï¼Atlantoaxial Dislocation (AAD) was enacted by the academic committee of spine surgery of integrated traditional Chinese and Western medicine. The guideline's recommendations forms by evidence-based medicine and the expert consensus of Integrative Medicine. The guidement principles is "spinal cord decompression, reconstruction of atlantoaxial stability". The objective of the guideline is providing an academic suggestion. The main contents include diagnostic criteria, traditional Chinese medicine's (TCM) dialectical method, clinical classification, treatment strategies and methods.
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Medicina Integrativa , Luxaciones Articulares , Descompresión Quirúrgica , Humanos , Medicina Tradicional ChinaRESUMEN
Growing reports indicate that long noncoding RNA (lncRNA) are involved in the regulation of various biological processes of cancer cells. LINC00319 is an ill investigated lncRNA and has been shown to regulate lung cancer, nasopharyngeal carcinoma and ovarian cancer. Nevertheless, its roles in bladder cancer (BCa) remain unclear. In our research, LINC00319 was shown to be an upregulated lncRNA in BCa tissues. LINC00319 expression is negatively correlated with the patient's prognosis. Silencing of LINC00319 suppressed BCa proliferation and invasiveness. In addition, the data indicated LINC00319 was a sponge for miR-4492 and miR-4492 suppressed ROMO1 expression in BCa. Furthermore, our results illustrated miR-4492/ROMO1 axis regulates proliferation, migration, and invasion and LINC00319 exerts oncogenic roles through modulating miR-4492/ROMO1 axis. In sum, this study suggested that LINC00319 acts as oncogenic roles in BCa progression.