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The detection of nucleic acid sequences in parallel with the discrimination of single nucleotide variations (SNVs) is critical for research and clinical applications. A few limitations make the detection technically challenging, such as too small variation in probe-hybridization energy caused by SNVs, the non-specific amplification of false nucleic acid fragments and the few options of dyes limited by spectral overlaps. To circumvent these limitations, we developed a single-molecule nucleic acid detection assay without amplification or fluorescence termed THREF (hybridization-induced tandem DNA hairpin refolding failure) based on multiplexed magnetic tweezers. THREF can detect DNA and RNA sequences at femtomolar concentrations within 30 min, monitor multiple probes in parallel, quantify the expression level of miR-122 in patient tissues, discriminate SNVs including the hard-to-detect G-U or T-G wobble mutations and reuse the probes to save the cost. In our demonstrative detections using mock clinic samples, we profiled the let-7 family microRNAs in serum and genotyped SARS-CoV-2 strains in saliva. Overall, the THREF assay can discriminate SNVs with the advantages of high sensitivity, ultra-specificity, multiplexing, reusability, sample hands-free and robustness.
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Técnicas Genéticas , Polimorfismo Genético , ARN , Humanos , COVID-19/diagnóstico , ADN/genética , Mutación , SARS-CoV-2/genética , ARN/análisisRESUMEN
Deubiquitinases are a group of proteins that identify and digest monoubiquitin chains or polyubiquitin chains attached to substrate proteins, preventing the substrate protein from being degraded by the ubiquitin-proteasome system. Deubiquitinases regulate cellular autophagy, metabolism and oxidative stress by acting on different substrate proteins. Recent studies have revealed that deubiquitinases act as a critical regulator in various cardiac diseases, and control the onset and progression of cardiac disease through a board range of mechanism. This review summarizes the function of different deubiquitinases in cardiac disease, including cardiac hypertrophy, myocardial infarction and diabetes mellitus-related cardiac disease. Besides, this review briefly recapitulates the role of deubiquitinases modulators in cardiac disease, providing the potential therapeutic targets in the future.
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Infarto del Miocardio , Ubiquitina , Humanos , Ubiquitina/metabolismo , Poliubiquitina/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Enzimas Desubicuitinizantes/genéticaRESUMEN
In brief: The mechanism underlying the accumulation of γδT cells in the decidua, which helps maintain maternal-fetal immunotolerance in early pregnancy, is unknown. This study reveals that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua. Abstract: Decidual γδT (dγδT) cells help maintain maternal-fetal immunotolerance in early pregnancy. However, the mechanism underlying the accumulation of γδT cells in the decidua is unknown. Previous work showed that RANKL upregulated intercellular adhesion molecule 1 (ICAM-1) in decidual stromal cells (DSCs), and Rankl knockout mice had limited dγδT cell populations. In this study, we measured the expression levels of RANKL/RANK and ICAM-1 in DSCs, in addition to the integrins of ICAM-1 on dγδT cells, and the number of dγδT cells from patients with recurrent spontaneous abortion (RSA) and normal pregnant women in the first trimester. RSA patients showed significantly decreased RANKL/RANK and ICAM-1/CD11a signaling in decidua, and a decreased percentage of dγδT cells, which was positively correlated with DSC-derived RANKL and ICAM-1. Next, an in vitro adhesion experiment showed that the enhanced attraction of human DSCs to dγδT cells after RANKL overexpression was almost completely aborted by anti-ICAM-1. Furthermore, Rankl knockout mice showed a significant reduction in NF-κB activity compared with wild-type controls. Finally, we applied a selective NF-κB inhibitor named PDTC to validate the role of NF-κB in RANKL-mediated ICAM-1 upregulation. Taken together, our data show that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua. A reduction in RANKL/ICAM-1 signaling in DSCs may result in insufficient accumulation of γδT cells in decidua and, in turn, RSA.
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Decidua , Molécula 1 de Adhesión Intercelular , FN-kappa B , Ligando RANK , Regulación hacia Arriba , Adulto , Animales , Femenino , Humanos , Ratones , Embarazo , Decidua/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Molécula 1 de Adhesión Intercelular/genética , Ratones Noqueados , FN-kappa B/metabolismo , Ligando RANK/metabolismo , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Transducción de Señal , Células del Estroma/metabolismo , Linfocitos T/metabolismoRESUMEN
PURPOSE: To summarize the findings of relevant randomized controlled trials (RCTs) and conduct a meta-analysis to investigate the potential effect of aromatase inhibitors on preventing moderate to severe ovarian hyperstimulation syndrome (OHSS) in infertile women undergoing in vitro fertilization (IVF). METHODS: We searched for relevant RCTs in electronic databases, including MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov (from inception to August 2023). In addition, we manually searched the related reviews and reference lists of included studies for further relevant studies. We included RCTs where aromatase inhibitors prescribed either during controlled ovarian stimulation (COS) or in early luteal phase. The meta-analysis was performed using RevMan 5.4.1 software. The primary outcome was the incidence of moderate to severe OHSS. A descriptive analysis was conducted in cases where a meta-analysis was not feasible due to heterogeneity or lack of comparable data. RESULTS: 2858 records were retrieved and 12 RCTs were finally included. Letrozole was administered in the treatment group during COS in seven RCTs, whereas in the early luteal phase in five RCTs. Compared with the control group, the risk of moderate to severe OHSS significantly reduced by 55% in the letrozole group (RR 0.45, 95% CI 0.32 to 0.64, I2 = 0%, 5 RCTs, 494 patients). Moreover, serum estradiol (E2) levels on hCG trigger day significantly decreased with the administration of letrozole during COS (MD -847.23, 95% CI -1398.00 to -296.47, I2 = 93%, 5 RCTs, 374 patients). And serum E2 levels on the 4th, 5th and 7th to 10th day after hCG trigger were also significantly lower than those in the control group when letrozole was administered in the early luteal phase. CONCLUSIONS: Patients with high risk of OHSS probably benefit from letrozole, which has been revealed to reduce the incidence of moderate to severe OHSS by this systematic review. However, the very limited number of participants and the quality of the included studies does not allow to recommend letrozole for the prevention of severe OHSS.
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Inhibidores de la Aromatasa , Fertilización In Vitro , Infertilidad Femenina , Síndrome de Hiperestimulación Ovárica , Inducción de la Ovulación , Femenino , Humanos , Embarazo , Inhibidores de la Aromatasa/administración & dosificación , Inhibidores de la Aromatasa/uso terapéutico , Fertilización In Vitro/métodos , Infertilidad Femenina/prevención & control , Infertilidad Femenina/etiología , Letrozol/uso terapéutico , Letrozol/administración & dosificación , Síndrome de Hiperestimulación Ovárica/prevención & control , Síndrome de Hiperestimulación Ovárica/epidemiología , Síndrome de Hiperestimulación Ovárica/etiología , Inducción de la Ovulación/métodos , Inducción de la Ovulación/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: For patients with rectal cancer, the utilization of temporary ileostomy (TI) has proven effective in minimizing the occurrence of severe complications post-surgery, such as anastomotic leaks; however, some patients are unable to reverse in time or even develop a permanent stoma (PS). We aimed to determine the preoperative predictors associated with TS failure and develop and validate appropriate predictive models to improve patients' quality of life. METHODS: This research included 403 patients with rectal cancer who underwent temporary ileostomies between January 2017 and December 2021. All patients were randomly divided into either the developmental (70%) or validation (30%) group. The independent risk factors for PS were determined using univariate and multivariate logistic regression analyses. Subsequently, a nomogram was constructed, and the prediction probability was estimated by calculating the area under the curve (AUC) using receiver operating characteristic (ROC) analysis. A calibration plot was used to evaluate the nomogram calibration. RESULTS: Of the 403 enrolled patients, 282 were randomized into the developmental group, 121 into the validation group, and 58 (14.39%) had a PS. The development group consisted of 282 patients, of whom 39 (13.81%) had a PS. The validation group consisted of 121 patients, of whom, 19 (15.70%) had a PS; 37 related factors were analyzed in the study. Multivariate logistic regression analysis demonstrated significant associations between the occurrence of PS and various factors in this patient cohort, including tumor location (OR = 6.631, P = 0.005), tumor markers (OR = 2.309, P = 0.035), American Society of Anesthesiologists (ASA) score (OR = 4.784, P = 0.004), T4 stage (OR = 2.880, P = 0.036), lymph node metastasis (OR = 4.566, P = 0.001), and distant metastasis (OR = 4.478, P = 0.036). Furthermore, a preoperative nomogram was constructed based on these data and subsequently validated in an independent validation group. CONCLUSION: We identified six independent preoperative risk factors associated with PS following rectal cancer resection and developed a validated nomogram with an area under the ROC curve of 0.7758, which can assist surgeons in formulating better surgical options, such as colostomy, for patients at high risk of PS.
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Ileostomía , Nomogramas , Neoplasias del Recto , Humanos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Femenino , Masculino , Ileostomía/efectos adversos , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Factores de Riesgo , Estomas Quirúrgicos/efectos adversos , Calidad de Vida , Curva ROC , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , AdultoRESUMEN
Viral infections are common in children. Many can be asymptomatic or have delayed health consequences. In view of increasing availability of point-of-care viral detection technologies, with possible application in newborn screening, this review aimed to (1) identify potentially asymptomatic viruses detectable in infants under one year old, via saliva/nasopharyngeal swab, and (2) describe associations between viruses and long-term health conditions. We systematically searched Embase(Ovid), Medline(Ovid) and PubMed, then further searched the literature in a tiered approach. From the 143 articles included, 28 potentially asymptomatic viruses were identified. Our second search revealed associations with a range of delayed health conditions, with most related to the severity of initial symptoms. Many respiratory viruses were linked with development of recurrent wheeze or asthma. Of note, some potentially asymptomatic viruses are linked with later non-communicable diseases: adenovirus serotype 36 and obesity, Enterovirus-A71 associated Hand, Foot, Mouth Disease and Attention-Deficit Hyperactivity Disorder, Ebstein Barr Virus (EBV) and malignancy, EBV and multiple sclerosis, HHV-6 and epilepsy, HBoV-1 and lung fibrosis and Norovirus and functional gastrointestinal disorders. Our review identified many potentially asymptomatic viruses, detectable in early life with potential delayed health consequences, that could be important to screen for in the future using rapid point-of-care viral detection methods. IMPACT: Novel point-of-care viral detection technologies enable rapid detection of viruses, both old and emerging. In view of increasing capability to screen for viruses, this is the first review to explore which potentially asymptomatic viruses, that are detectable using saliva and/or nasopharyngeal swabs in infants less than one year of age, are associated with delayed adverse health conditions. Further research into detecting such viruses in early life and their delayed health outcomes may pave new ways to prevent non-communicable diseases in the future.
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Infecciones por Enterovirus , Enfermedades no Transmisibles , Virosis , Virus , Lactante , Recién Nacido , Niño , Humanos , SalivaRESUMEN
BACKGROUND: Inequalities in job opportunities and income prompts many Chinese parents to leave rural regions to work in urban regions. Their children are left behind in rural regions, subjected to worse quality of childcare that jeopardizes their development. This study aimed to examine the association between quality of childcare and delayed child development in under-three years children left behind in China. METHODS: Cross-sectional national survey was conducted in children left behind in rural China in 2017. Exploratory and confirmatory factor analysis was used to develop a quality of childcare index. Mutlilevel analyses determined factors associated with quality of childcare and child development on a province and individual level. RESULT: The largest population of at-risk children left behind were found in higher-GDP provinces. Children left behind had the lowest mean quality of childcare score. Multilevel analysis found that province level accounted for a great proportion of variance observed. CONCLUSIONS: While migration to urban regions for work may improve household income, a trade-off in worse quality of childcare and developmental delays exists. With improving household income often being the greatest contributing factor for parental migration, policies to reduce inequalities in job opportunities and wealth between rural and urban regions are required. IMPACT: Previous studies identified higher prevalence of developmental delays in children left behind in China. However, quality of childcare has not been examined. Based on WHO's Nurturing Care Framework, we developed a quality of childcare index to assess its association with child development in children left behind. Greatest proportion of children left behind at-risk of developmental delays resided in higher-GDP states, indicating a trade-off in worse quality of childcare and developmental delays. Since improving household income is the main factor for parental migration, policies to close inequalities in job opportunities and wealth between rural and urban regions are required.
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Cuidado del Niño , Desarrollo Infantil , Niño , Humanos , Estudios Transversales , Renta , China/epidemiología , Población RuralRESUMEN
OBJECTIVES: To analyze the ability of magnetic resonance (MR) to identify cystic biliary atresia (CBA) and choledochal cyst (CC). METHODS: Infants (≤ 1 year old) who were diagnosed with CBA or CC type I/IV from January 2010 to July 2023 were retrospectively reviewed. Imaging characteristics on MR were compared between the CBA and CC groups. Binary logistic regression and the area under the receiver operating characteristic curve (AUC) were analyzed for the identification of CBA. RESULTS: Sixty-three patients with CBA (median age, 30 days) and 172 patients with CC (median age, 60 days) were included. Gallbladder (GB) wall thickness (cutoff, 1.2 mm) showed 98.4% sensitivity and 100% specificity (AUC, 0.998). MR-triangular cord thickness (MR-TCT) (cutoff, 4.1 mm) showed 100% sensitivity and 95.9% specificity (AUC, 0.986). The bile duct loop visualization showed 96.8% sensitivity and 100% specificity (AUC, 0.984). Proximal bile duct (PBD) diameter (cutoff, 1.3 mm) showed 92.1% sensitivity and 95.3% specificity (AUC, 0.977). Cyst wall thickness (cutoff, 1 mm) showed 77.8% sensitivity and 95.3% specificity (AUC, 0.942). The combination of GB wall thickness > 1.2 mm and MR-TCT > 4.1 mm, GB wall thickness > 1.2 mm and loop visualization, GB wall thickness > 1.2 mm, and cyst wall thickness > 1 mm showed 100% sensitivity and 100% specificity (AUC, 1.000). CONCLUSIONS: Imaging characteristics on MR might be used to identify CBA and CC, and the combination of GB wall thickness and MR-TCT, or loop visualization, or cyst wall thickness, has a perfect diagnostic value. CLINICAL RELEVANCE STATEMENT: Early and accurate differentiation of CBA and CC is essential, but current methods rely on inherently subjective ultrasound. Biliary features on MRI allow for an objective, accurate diagnosis.
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Osteoporotic bone defects, a severe complication of osteoporosis, are distinguished by a delayed bone healing process and poor repair quality. While bone marrow-derived mesenchymal stem cells (BMMSCs) are the primary origin of bone-forming osteoblasts, their mitochondrial function is impaired, leading to inadequate bone regeneration in osteoporotic patients. Melatonin is well-known for its antioxidant properties and regulation on bone metabolism. The present study postulated that melatonin has the potential to enhance the repair of osteoporotic bone defects by restoring the mitochondrial function of BMMSCs. In vitro administration of melatonin at varying concentrations (0.01, 1, and 100 µM) demonstrated a significant dose-dependent improvement in the mitochondrial function of BMMSCs obtained from ovariectomized rats (OVX-BMMSCs), as indicated by an elevation in mitochondrial membrane potential, adenosine triphosphate synthesis and expression of mitochondrial respiratory chain factors. Melatonin reduced the level of mitochondrial superoxide by activating the silent information regulator type 1 (SIRT1) and its downstream antioxidant enzymes, particularly superoxide dismutase 2 (SOD2). The protective effects of melatonin were found to be nullified upon silencing of Sirt1 or Sod2, underscoring the crucial role of the SIRT1-SOD2 axis in the melatonin-induced enhancement of mitochondrial energy metabolism in OVX-BMMSCs. To achieve a sustained and localized release of melatonin, silk fibroin scaffolds loaded with melatonin (SF@MT) were fabricated. The study involved the surgical creation of bilateral femur defects in OVX rats, followed by the implantation of SF@MT scaffolds. The results indicated that the application of melatonin partially restored the mitochondrial energy metabolism and osteogenic differentiation of OVX-BMMSCs by reinstating mitochondrial redox homeostasis. These findings suggest that the localized administration of melatonin through bone implants holds potential as a therapeutic approach for addressing osteoporotic bone defects.
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Melatonina , Células Madre Mesenquimatosas , Osteoporosis , Humanos , Ratas , Animales , Osteogénesis , Melatonina/metabolismo , Sirtuina 1/metabolismo , Antioxidantes/uso terapéutico , Médula Ósea/metabolismo , Osteoporosis/tratamiento farmacológico , Diferenciación Celular , Mitocondrias/metabolismo , Células CultivadasRESUMEN
BACKGROUND: The retinal pigment epithelium (RPE) is essential for retinal homeostasis. Comprehensively exploring the transcriptional patterns of diabetic human RPE promotes the understanding of diabetic retinopathy (DR). METHODS AND RESULTS: A total of 4125 differentially expressed genes (DEGs) were screened out from the human primary RPE cells subjected to prolonged high glucose (HG). The subsequent bioinformatics analysis is divided into 3 steps. In Step 1, 21 genes were revealed by intersecting the enriched genes from the KEGG, WIKI, and Reactome databases. In Step 2, WGCNA was applied and intersected with the DEGs. Further intersection based on the enrichments with the GO biological processes, GO cellular components, and GO molecular functions databases screened out 12 candidate genes. In Step 3, 13 genes were found to be simultaneously up-regulated in the DEGs and a GEO dataset involving human diabetic retinal tissues. VEGFA and ERN1 were the 2 starred genes finally screened out by overlapping the 3 Steps. CONCLUSION: In this study, multiple genes were identified as crucial in the pathological process of RPE under protracted HG, providing potential candidates for future researches on DR. The current study highlights the importance of RPE in DR pathogenesis.
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Retinopatía Diabética , Retina , Humanos , Retinopatía Diabética/genética , Células Epiteliales , Pigmentos Retinianos , GlucosaRESUMEN
BACKGROUND: The association of hypertension and depression with mortality has not been fully understood. We aimed to explore the possible independent or joint association of hypertension and depression with mortality. Their interaction effects on mortality and possible mediating role were also investigated. METHODS: Associations of hypertension, depression, and their interaction with all-cause and cardiovascular disease (CVD) mortality were evaluated using multivariate Cox proportional hazards regression models. The mediation analysis was conducted with a Sobel test. RESULTS: A total of 35152 participants were included in the final analysis. Hypertension and depression were independently associated with increased risk of all-cause and CVD mortality. The co-existence of hypertension and depression resulted in a 1.7-fold [95% confidence interval (CI): 1.3-2.1] increase in all-cause mortality and a 2.3-fold (95% CI: 1.4-3.7) increase in CVD mortality compared to those with neither of them. Hypertension and depression showed no significant multiplicative (P for interaction, 0.587) and additive interaction (P for relative excess risk of interaction, 0.243; P for Interaction on additive scale, 0.654) on all-cause mortality, as well as on CVD mortality. Depression did not mediate the relationship between hypertension and all-cause (Z=1.704, P=0.088) and CVD mortality (Z=1.547, P=0.122). Hypertension did not mediate the relationship between all-cause and CVD mortality as well. CONCLUSION: Hypertension and depression were related to all-cause and CVD mortality independently and the co-existence of them increased the risk of mortality. However, there is no interaction effect of them on mortality, and hypertension or depression did not mediate the association of each other with mortality.
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Enfermedades Cardiovasculares , Hipertensión , Humanos , Depresión/complicaciones , Hipertensión/complicaciones , Riesgo , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
BACKGROUND: Lung cancer remains a major global health concern due to its high incidence and mortality rates. With advancements in medical treatments, an increasing number of early-stage lung cancer cases are being detected, making surgical treatment the primary option for such cases. However, this presents challenges to the physical and mental recovery of patients. Peplau known as the "mother of psychiatric associations" has formulated a theory of interpersonal relationships in nursing. Through effective communication between nurses and patients over four periods, she has established a good therapeutic nurse-patient relationship. Therefore, this study aimed to explore the effect of perioperative multimodal nursing based on Peplau's interpersonal relationship theory on the rehabilitation of patients with surgical lung cancer. METHODS: We retrospectively analyzed 106 patients with non-small cell lung cancer who underwent thoracoscopic lobectomy at our department between June 2021 and April 2022. Patients were categorized into two groups according to the different nursing intervention techniques. The Peplau's group comprised 53 patients who received targeted nursing interventions, and the control group comprised 53 patients who received conventional nursing care. We observed the patients' illness uncertainty, quality of life, and clinical symptoms in both groups. RESULTS: Patients in the Peplau's group had significantly lower illness uncertainty scores and a significantly higher quality of recovery than those in the control group. However, there were no significant differences in length of post-anesthesia care unit stay, complication rates, and visual analog scores between both groups. CONCLUSION: The multimodal perioperative nursing based on Peplau's interpersonal relationship theory not only reduces the illness uncertainty of patients with lung cancer surgery and improves their QoR but also expands the application of this theory in clinical practice, guiding perioperative nursing of patients with lung cancer. IMPLICATIONS: These findings provide practical information for standardized care in a hectic anesthetic care setting. IMPACT: The assessed anesthesia nursing model helps reduce uncertainty and promote early recovery in patients with cancer at various stages of their disease, which expands the scope of therapeutic practice and existing theories. It also serves as a guide for care in the anesthesia recovery room. REPORTING METHOD: We adhered to the relevant Equator guidelines and the checklist of items in the case-control study report. PATIENT OR PUBLIC CONTRIBUTION: Patients cooperated with medical staff to complete relevant scales.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Femenino , Humanos , Teoría de Enfermería , Estudios Retrospectivos , Estudios de Casos y Controles , Neoplasias Pulmonares/cirugía , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Calidad de VidaRESUMEN
BACKGROUND: Temporary ileostomy (TI) has proven effective in reducing the severity of anastomotic leakage after rectal cancer surgery; however, some ileostomies fail to reverse over time, leading to conversion into a permanent stoma (PS). In this study, we aimed to investigate the preoperative risk factors and cumulative incidence of TI non-closure after sphincter-preserving surgery for rectal cancer. MATERIALS AND METHODS: We conducted a meta-analysis after searching the Embase, Web of Science, PubMed, and MEDLINE databases from their inception until November 2023. We collected all published studies on the risk factors related to TI non-closure after sphincter-preserving surgery for rectal cancer. RESULTS: A total of 1610 studies were retrieved, and 13 studies were included for meta-analysis, comprising 3026 patients. The results of the meta-analysis showed that the identified risk factors included older age (p = 0.03), especially > 65 years of age (p = 0.03), male sex (p = 0.009), American Society of Anesthesiologists score ≥ 3 (p = 0.004), comorbidity (p = 0.001), and distant metastasis (p < 0.001). Body mass index, preoperative hemoglobin, preoperative albumin, preoperative carcinoma embryonic antigen, tumor location, neoadjuvant chemoradiotherapy, smoking, history of abdominal surgery, and open surgery did not significantly change the risk of TI non-closure. CONCLUSION: We identified five preoperative risk factors for TI non-closure after sphincter-preserving surgery for rectal cancer. This information enables surgeons to identify high-risk groups before surgery, inform patients about the possibility of PS in advance, and consider performing protective colostomy or Hartmann surgery.
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Neoplasias del Recto , Estomas Quirúrgicos , Humanos , Masculino , Ileostomía/efectos adversos , Incidencia , Factores de Riesgo , Neoplasias del Recto/cirugíaRESUMEN
The aim of this study is to conduct a thorough evaluation of the association between Benzophenone-3 (BP-3) exposure and OA, offering critical insights into the underlying mechanisms involved. The National Health and Nutrition Examination Survey (NHANES) database was utilized to investigate the correlation between BP-3 and osteoarthritis. Proteomic sequencing from clinical sample and the PharmMapper online tool were employed to predict the biological target of BP-3. Cellular molecular assays and transfection studies were performed to verify the prediction from bioinformatics analyses. Through cross-sectional analysis of the NHANES database, we identified BP-3 as a risk factor for OA development. The results of proteomic sequencing showed that Secreted Protein Acidic and Rich in Cysteine (SPARC) was significantly elevated in the area of damage compared to the undamaged area. SPARC was also among the potential biological targets of BP-3 predicted by the online program. Through in vitro cell experiments, we further determined that the toxicological effects of BP-3 may be due to SPARC, which elevates intracellular GPX4 levels, activates the glutathione system, and promotes lipid peroxidation to mitigate ferroptosis. Inhibiting SPARC expression has been shown to reduce inflammation and ferroptosis in OA contexts. This research provides an expansive understanding of BP-3's influence on osteoarthritis development. We have identified SPARC as a potent target for combating chondrocyte ferroptosis in BP-3-associated osteoarthritis.
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Benzofenonas , Ferroptosis , Osteoartritis , Osteonectina , Humanos , Benzofenonas/metabolismo , Benzofenonas/toxicidad , Biología Computacional , Estudios Transversales , Ferroptosis/efectos de los fármacos , Encuestas Nutricionales , Osteoartritis/inducido químicamente , Osteonectina/antagonistas & inhibidores , Osteonectina/genética , Osteonectina/metabolismo , ProteómicaRESUMEN
Superenhancers (SEs) are large genomic regions with a high density of enhancer marks. In cancer, SEs are found near oncogenes and dictate cancer gene expression. However, how oncogenic SEs are regulated remains poorly understood. Here, we show that INO80, a chromatin remodeling complex, is required for SE-mediated oncogenic transcription and tumor growth in melanoma. The expression of Ino80, the SWI/SNF ATPase, is elevated in melanoma cells and patient melanomas compared with normal melanocytes and benign nevi. Furthermore, Ino80 silencing selectively inhibits melanoma cell proliferation, anchorage-independent growth, tumorigenesis, and tumor maintenance in mouse xenografts. Mechanistically, Ino80 occupies >90% of SEs, and its occupancy is dependent on transcription factors such as MITF and Sox9. Ino80 binding reduces nucleosome occupancy and facilitates Mediator recruitment, thus promoting oncogenic transcription. Consistently, genes co-occupied by Ino80 and Med1 are selectively expressed in melanomas compared with melanocytes. Together, our results reveal an essential role of INO80-dependent chromatin remodeling in SE function and suggest a novel strategy for disrupting SEs in cancer treatment.
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Carcinogénesis/genética , Proteínas de Ciclo Celular/metabolismo , Elementos de Facilitación Genéticos/fisiología , Regulación Neoplásica de la Expresión Génica/genética , Melanoma/genética , Melanoma/fisiopatología , Proteínas Nucleares/metabolismo , Animales , Proteínas de Ciclo Celular/genética , Proliferación Celular/genética , Ensamble y Desensamble de Cromatina/genética , Silenciador del Gen , Xenoinjertos , Humanos , Subunidad 1 del Complejo Mediador/genética , Melanocitos/metabolismo , Melanoma/enzimología , Ratones , Proteínas Nucleares/genética , Unión Proteica , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: There is a deficiency in the evidence from rural and regional centres in Australia on the weekend effect following presentation with acute stroke. OBJECTIVE: To estimate the association between admission over a weekend/holiday and all-cause mortality 3-day, 7-day, 14-day, 1-month, 3-month, 6-month, and 12-month following acute stroke. METHODS: The records of stroke patients admitted to a main regional hospital in Australia from 2010 to 2020 were linked with the National Death Index. Time to death following ischaemic, haemorrhagic, and total stroke at different time points was modelled using Weibull, Exponential, or Gompertz regression based on best model fit determined by Akaike's information criterion. RESULTS: Of 1669 patients, 1273 (76.3%) were admitted on a weekday, and 396 (23.7%) on a weekend/ or holiday. After adjusting for age, sex, and Charlson Comorbidity Index, stroke type and country of birth, admissions over a weekend/holiday following total stroke were significantly associated with an increased risk of dying within three days from admission [hazard ratio (HR): 1.59, 95% confidence interval: 1.01-2.50]. In haemorrhagic stroke, increased risk of death was significantly higher at three days (HR: 2.19, 95% confidence interval: 1.17-4.08), 14 days (HR: 1.73, 95% confidence interval: 1.02-2.93), and 1 month (HR: 1.82, 95% confidence interval: 1.09-3.03) following admission on the weekend/ or holiday compared to those admitted during the weekdays. CONCLUSIONS: This study reports a short-term adverse weekend/holiday effect following admission for haemorrhagic stroke or total stroke. No significant weekend/holiday effect was found in ischaemic stroke.
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Vacaciones y Feriados , Accidente Cerebrovascular Isquémico , Admisión del Paciente , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Anciano , Factores de Tiempo , Estudios Retrospectivos , Factores de Riesgo , Anciano de 80 o más Años , Persona de Mediana Edad , Australia/epidemiología , Medición de Riesgo , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/terapia , Atención Posterior , Accidente Cerebrovascular Hemorrágico/mortalidad , Accidente Cerebrovascular Hemorrágico/diagnóstico , Accidente Cerebrovascular Hemorrágico/terapia , Mortalidad Hospitalaria , Causas de Muerte , PronósticoRESUMEN
BACKGROUND: Chinese giant salamander protein hydrolysates (CGSPH) are beneficial to human health as a result of their high content of amino acids and peptides. However, the formation of bitter peptides in protein hydrolysates (PHs) would hinder their application in food industry. The ultrasound assisted wet-heating Maillard reaction (MR) is an effective way to improve the flavor of PHs. Thus, the effect of ultrasonic assisted wet-heating MR on the structure and flavor of CGSPH was investigated in the present study. RESULTS: The results indicated that the ultrasound assisted wet-heating MR products (MRPs) exhibited a higher degree of graft and more significant changes in the secondary and tertiary structures of CGSPH compared to traditional wet-heating MRPs. Moreover, ultrasound assisted wet-heating MR could significantly increase the content of small molecule peptides and reduce the content of free amino acids of CGSPH, which resulted in more significant changes in flavor characteristics. The changed in flavor properties after MR (especially ultrasound assisted wet-heating MRPs) were mainly manifested by a significant reduction in bitterness, as well as a significant increase in the content of aromatic aldehyde ester compounds such as furan-2-carbaldehyde, butanal, benzaldehyde, furfural, etc. CONCLUSIONS: Ultrasound assisted wet-heating MR between CGSPH and xylose could be a promising way to improve the sensory characteristics of CGSPH. © 2024 Society of Chemical Industry.
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M1-like macrophages have been reported to play critical roles in acute kidney injury (AKI). Here, we elucidated the role of ubiquitin-specific protease 25 (USP25) in M1-like macrophages polarization and AKI. High USP25 expression was correlated with a decline in renal function in patients with acute kidney tubular injury and in mice with AKI. In contrast, USP25 knockout reduced M1-like macrophage infiltration, suppressed M1-like polarization, and improved AKI in mice, indicating that USP25 was necessary for M1-like polarization and proinflammatory response. Immunoprecipitation assay and liquid chromatography-tandem mass spectrometry showed that the M2 isoform of pyruvate kinase, muscle (PKM2) was a target substrate of USP25. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated the USP25 regulated aerobic glycolysis and lactate production during M1-like polarization via PKM2. Further analysis showed that the USP25-PKM2-aerobic glycolysis axis positively regulated M1-like polarization and exacerbated AKI in mice, providing potential therapeutic targets for AKI treatment.
Asunto(s)
Lesión Renal Aguda , Daño por Reperfusión , Ratones , Animales , Piruvato Quinasa/metabolismo , Riñón/metabolismo , Macrófagos/metabolismo , Daño por Reperfusión/metabolismo , Isquemia/metabolismo , Músculos , Reperfusión , Glucólisis , Ratones Endogámicos C57BL , Ubiquitina Tiolesterasa/metabolismoRESUMEN
SARS-CoV-2, especially the variant strains, is rapidly spreading around the world. Rapid detection methods for the virus are crucial for controlling the COVID-19 epidemic. Herein, a localized surface plasmonic resonance (LSPR) biosensor based on Ω-shaped fiber optic (Ω-FO) was developed for dual assays of SARS-CoV-2 monitoring. Due to its strong ability to control the orientation and density, a new T-shaped aptamer exhibits enhanced binding affinity toward N proteins. After being combined on the fiber optic surface, the T-shaped aptamer sensitively captured N proteins of SARS-CoV-2 for a direct assay. Further, core-shell structured gold/silver nanoparticles functionalized with a T-shaped aptamer (apt-Ag@AuNPs) can amplify the signal of N protein detection for a sandwich assay. The real-time analytical feature of the dual assays endows time-dependent sensitivity enhancement behavior, which provides a guideline to save analytical time. With those characteristics, the LSPR biosensor has been successfully used to rapidly identify 39 healthy volunteers and 39 COVID-19 patients infected with the ancestral or variant SARS-CoV-2. With the help of simple pretreatment, we obtain a true negative rate of 100% and a true positive rate of 92.3% with a short analysis time of 45 min using the direct assay. Further, the LSPR biosensor could also broaden the detection application range to the surface of cold-chain foods using a sandwich assay. Thus, the LSPR biosensor based on Ω-FO was demonstrated to have broad application potential to detect SARS-CoV-2 rapidly.
Asunto(s)
Técnicas Biosensibles , COVID-19 , Nanopartículas del Metal , Humanos , Resonancia por Plasmón de Superficie/métodos , SARS-CoV-2 , Oro , COVID-19/diagnóstico , Plata , Técnicas Biosensibles/métodos , OligonucleótidosRESUMEN
BACKGROUND: In recent years, several studies have demonstrated that stress hyperglycemia is significantly associated with poor prognosis in patients diagnosed with acute coronary syndrome (ACS). In the present study, we aimed to investigate the potential associations between various markers of stress hyperglycemia, such as admission blood glucose (ABG), fasting blood sugar (FBS), and stress hyperglycemia ratio (SHR) with different definitions, and the occurrence of adverse cardiovascular events in patients diagnosed with ST-elevation myocardial infarction (STEMI) who have undergone percutaneous coronary intervention (PCI). METHODS: Our study enrolled a total of 1099 patients diagnosed with STEMI who underwent PCI from 2016 to 2021. The primary outcomes of this study were in-hospital death and all-cause mortality. RESULTS: Stress hyperglycemia was associated with a higher incidence of in-hospital death (ABG OR: 1.27 95% CI 1.19-1.36; FBS OR: 1.25 95% CI 1.16-1.35; SHR1 OR: 1.61 95% CI 1.21-2.14; SHR2 OR: 1.57, 95%CI 1.22-2.01; SHR3 OR: 1.59, 95%CI 1.24-2.05) and all-cause mortality (ABG HR: 1.10, 95% CI 1.07-1.14; FBS HR: 1.12, 95 CI 1.07-1.17; SHR1 HR: 1.19 95% CI 1.03-1.39; SHR2 HR: 1.28, 95%CI 1.14-1.44; SHR3 HR: 1.29, 95%CI 1.14-1.45) after adjusting for ischemic time, age, gender, BMI, hypertension, hyperlipidemia, diabetes mellitus (DM), current smoking history, chronic kidney disease (CKD), previous history of coronary artery disease (CAD), atrial fibrillation (AF), heart failure (HF), stroke, cancer, culprit vessel, multi-vessel disease. These associations exhibited a non-linear, J-shaped pattern, wherein the risk significantly increased when the ABG and FBS levels exceeded 5mmol/L. Moreover, the inflection point for SHR was estimated to be 1.2. CONCLUSIONS: Stress hyperglycemia was significantly associated with an increased risk of in-hospital death and all-cause mortality in STEMI patients treated with PCI. Stress hyperglycemia should be considered a high-risk prognostic marker in all STEMI patients, regardless of with or without diabetes.