RESUMEN
General anesthesia shares many similarities with natural sleep in behavior and electroencephalogram (EEG) patterns. The latest evidence suggests that general anesthesia and sleep-wake behavior may share overlapping neural substrates. The GABAergic neurons in the basal forebrain (BF) have recently been demonstrated to play a key role in controlling wakefulness. It was hypothesized that BF GABAergic neurons may participate in the regulation of general anesthesia. Here, using in vivo fiber photometry, we found that the activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia, having obviously decreased during the induction of anesthesia and being gradually restored during the emergence from anesthesia, in Vgat-Cre mice of both sexes. Activation of BF GABAergic neurons with chemogenetic and optogenetic approaches decreased sensitivity to isoflurane, delayed induction, and accelerated emergence from isoflurane anesthesia. Optogenetic activation of BF GABAergic neurons decreased EEG δ power and the burst suppression ratio (BSR) during 0.8% and 1.4% isoflurane anesthesia, respectively. Similar to the effects of activating BF GABAergic cell bodies, photostimulation of BF GABAergic terminals in the thalamic reticular nucleus (TRN) also strongly promoted cortical activation and behavioral emergence from isoflurane anesthesia. Collectively, these results showed that the GABAergic BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthesia via the GABAergic BF-TRN pathway. Our findings may provide a new target for attenuating the depth of anesthesia and accelerating emergence from general anesthesia.SIGNIFICANCE STATEMENT The basal forebrain (BF) is a key brain region controlling sleep-wake behavior. Activation of GABAergic neurons in the BF potently promotes behavioral arousal and cortical activity. Recently, many sleep-wake-related brain structures have been reported to participate in the regulation of general anesthesia. However, it is still unclear what role BF GABAergic neurons play in general anesthesia. In this study, we aim to reveal the role of BF GABAergic neurons in behavioral and cortical emergence from isoflurane anesthesia and elucidate the underlying neural pathways. Understanding the specific role of BF GABAergic neurons in isoflurane anesthesia would improve our understanding of the mechanisms of general anesthesia and may provide a new strategy for accelerating emergence from general anesthesia.
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Prosencéfalo Basal , Isoflurano , Masculino , Femenino , Ratones , Animales , Isoflurano/farmacología , Prosencéfalo Basal/fisiología , Neuronas GABAérgicas/fisiología , Sueño/fisiología , Electroencefalografía , Anestesia GeneralRESUMEN
PURPOSE: Universal germline testing in patients with colorectal cancer (CRC) with a multigene panel can detect various hereditary cancer syndromes. This study was performed to understand how to choose a testing panel and whether the result would affect clinical management. METHODS: We prospectively enrolled 486 eligible patients with CRC, including all patients with CRC diagnosed under age 70 years and patients with CRC diagnosed over 70 years with hereditary risk features between November 2017 and January 2018. All participants received germline testing for various hereditary cancer syndromes. RESULTS: The prevalence of germline pathogenic variants (PVs) in cancer susceptibility genes was 7.8% (38/486), including 25 PVs in genes with high-risk CRC susceptibility (the minimal testing set) and 13 PVs in genes with moderate-risk CRC susceptibility or increased cancer risk other than CRC (the additional testing set). All the clinically relevant PVs were found in patients diagnosed under age 70 years. Among them, 11 patients would not have been diagnosed if testing reserved to present guidelines. Most (36/38) of the patients with PVs benefited from enhanced surveillance and tailored treatment. PVs in genes from the minimal testing set were found in all age groups, while patients carried PVs in genes from the additional testing set were older than 40 years. CONCLUSION: Universal germline testing for cancer susceptibility genes should be recommended among all patients with CRC diagnosed under age 70 years. A broad panel including genes from the additional testing set might be considered for patients with CRC older than 40 years to clarify inheritance risks. TRIAL REGISTRATION NUMBER: NCT03365986.
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Neoplasias Colorrectales , Síndromes Neoplásicos Hereditarios , Adulto , Anciano , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Células Germinativas , Mutación de Línea Germinal/genética , Humanos , Síndromes Neoplásicos Hereditarios/genéticaRESUMEN
BACKGROUND: Sleep deprivation (SD) has become a serious concern worldwide. This study aimed to identify key modules and candidate hub genes correlated with diseases caused by SD, using co-expression analysis. METHODS: The weighted gene co-expression network analysis was performed to construct a co-expression network of hub genes correlated with SD. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to search for signaling pathways. The protein-protein interaction network analysis of central genes was performed to recognize the interactions among central genes. Molecular Complex Detection, a plugin in Cytoscape, was used to discover the hub gene clusters involved in SD. RESULTS: A total of 564 genes in the yellow module were identified based on the results of topological overlap measure-based clustering. The yellow module showed a pivotal correlation with SD. Six hub gene clusters prominently associated with SD were identified. Heat shock protein family and circadian clock genes among them may be the hub genes involved in SD. CONCLUSIONS: These genes and pathways might become therapeutic targets with clinical usefulness in the future.
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Perfilación de la Expresión Génica , Redes Reguladoras de Genes/genética , Transducción de Señal/genética , Privación de Sueño/genética , HumanosRESUMEN
BACKGROUND: BRD4 and PIN1 have been described to be involved in inflammation and vascular endothelial cell dysfunction, which in turn may increase pulse pressure. HYPOTHESIS: Genetic mutations within the BRD4 and PIN1 genes could affect the risk of high pulse pressure. METHODS: A total of four single nucleotide polymorphisms (SNPs) (BRD4: rs4808278; PIN1: rs2233678, rs2287838, and rs2233682) were genotyped in a cohort of 666 hypertensive patients and 232 normotensive controls with Chinese Han origin. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among the four SNPs within the BRD4 and PIN1 genes and diabetes. Logistic regression analysis was performed to calculate the odds ratio (ORs) (95% confidence interval (CI)) for the association between the four SNPs. RESULTS: Adjusted for age, weight, waist circumference, drinking, smoking, hypertension, and diabetes, high pulse pressure risk was significantly higher for carriers with the rs4808278-TT genotype in BRD4 than those with wild genotypes (OR: 0.400, 95% CI: 0.217-0.737, P* < 0.05). However, we did not find any significant association of rs2233678, rs2287838, and rs2233682 in PIN1 with high pulse pressure susceptibility after covariate adjustment. GMDR analysis indicated a significant three-locus model (P = 0.0107) involving rs4808278, rs2233678, and diabetes, the cross-validation consistency of the three-locus models was 9/10, and the testing accuracy was 57.47%. CONCLUSIONS: Genetic mutations within BRD4 (rs4808278) could affect the susceptibility to high pulse pressure in a southeastern Chinese population.
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Presión Sanguínea/genética , Proteínas de Ciclo Celular/genética , Hipertensión/genética , Peptidilprolil Isomerasa de Interacción con NIMA/genética , Polimorfismo de Nucleótido Simple , Factores de Transcripción/genética , Adulto , Anciano , Pueblo Asiatico/genética , China/epidemiología , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Hipertensión/diagnóstico , Hipertensión/etnología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Fenotipo , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
Oxidative stress caused by chronic intermittent hypoxia (CIH) is the hallmark of obstructive sleep apnea (OSA). Among the first line of defense against oxidative stress is the dismutation of superoxide radicals, which in the mitochondria is carried out by manganese superoxide dismutase (SOD2). In this study, wild-type (WT) and SOD2-heterozygous knockout (SOD2+/-) mice were exposed to CIH or normoxic (Nor) conditions. After 4 weeks, pulmonary artery pressure was measured, and the mice were processed to harvest either serum for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that heterozygous deletion of SOD2 markedly deteriorated pulmonary remodeling and increased the oxidative stress, especially promoted the infiltration of macrophages in the lungs of CIH mouse. Moreover, in the intermittent hypoxia (IH)-treated RAW264.7 cells, SOD2 knockdown increased the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation accompanied with the IL-1ß elevation and caspase-1 activity. Additionally, mitochondrial ROS (mtROS) scavenger mito-TEMPO abolished NLRP3 inflammasome activation in IH-treated RAW264.7 cells. Collectively, our results supported that SOD2 contributed to the pathogenesis of CIH-induced lung remodeling. Meanwhile, SOD2 knockdown exacerbates oxidative damage through assembly and activation of NLRP3 inflammasome in macrophages. SOD2 may be a novel therapeutic target for CIH-induced pulmonary inflammation and arteriole remodeling.
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Hipoxia/complicaciones , Inflamación/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Transducción de Señal/fisiología , Superóxido Dismutasa/deficiencia , Remodelación Vascular/fisiología , Animales , Eliminación de Gen , Humanos , Inflamasomas/metabolismo , Inflamación/epidemiología , Inflamación/genética , Pulmón , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/metabolismo , Estrés Oxidativo/genética , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Apnea Obstructiva del Sueño/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Remodelación Vascular/genéticaRESUMEN
The objective of this study was to describe prehospital delay and health beliefs in Chinese patients with colorectal cancer. A total of 756 adult Chinese patients with a first-time diagnosis of colorectal cancer were recruited during 2016 in Guangzhou, China. All patients completed the Chinese-language version of a questionnaire developed specifically for this study as well as the Chinese-language version of the Champion Health Belief Model Scale. The results of this study showed that the median length of the prehospital delay was 12 weeks and that the average delay was 18.29 (SD = 14.66) weeks. The rate of prehospital delay was 47.35%. The score of health beliefs among these patients was 115.56 (SD = 9.00) and the average score of the entries was 3.21 (SD = 0.25). Health beliefs about colorectal cancer were negatively correlated with prehospital delay. A multiple logistic regression showed that the level of health beliefs, frequency of physical examinations, occupation, and the site of the cancer were the major factors influencing prehospital delay (p < .05). The patients had a low rate of physical examination (41.40%), and colorectal cancer screening was not routine prior to their physical examination. This study showed that the incidence of prehospital delay among Chinese patients with colorectal cancer was 47.35%. Multiple factors influenced prehospital delay among Chinese patients with colorectal cancer.
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Pueblo Asiatico/psicología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/psicología , Conocimientos, Actitudes y Práctica en Salud , Hospitalización , Aceptación de la Atención de Salud , Adulto , Anciano , Anciano de 80 o más Años , China , Neoplasias Colorrectales/terapia , Estudios Transversales , Detección Precoz del Cáncer , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prevalencia , Encuestas y CuestionariosRESUMEN
The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAFV600E mutation test and germline sequencing. Among the 3250 eligible patients, MMR protein deficiency (dMMR) was detected in 330 (10.2%) patients. Ninety-three patients (2.9%) were diagnosed with LS. Nine (9.7%) patients with LS fulfilled Amsterdam criteria II and 76 (81.7%) met the revised Bethesda guidelines. Only 15 (9.7%) patients with absence of MLH1 on IHC had BRAFV600E mutation. One third (33/99) of the MMR gene mutations have not been reported previously. The age of onset indicates risk of LS in patients with dMMR tumors. For patients older than 65 years, only 2 patients (5.7%) fulfilling revised Bethesda guidelines were diagnosed with LS. Selective sequencing of all cases with dMMR diagnosed at or below age 65 years and only of those dMMR cases older than 65 years who fulfill revised Bethesda guidelines results in 8.2% fewer cases requiring germline testing without missing any LS diagnoses. While the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of constitutional mutations and frequency of BRAFV600E mutation is different. Patients older than 65 years who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population.
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Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Reparación de la Incompatibilidad de ADN/genética , Tamizaje Masivo/métodos , Homólogo 1 de la Proteína MutL/genética , Proteínas Proto-Oncogénicas B-raf/genética , Adulto , Anciano , Biomarcadores de Tumor/genética , China/epidemiología , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Variaciones en el Número de Copia de ADN/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Mutación de Línea Germinal/genética , Humanos , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
Four new steroidal saponins, 3-O-ß-D-glucopyranosyl(1â4)-ß-D-fucopyranosyl -(25R)-spirost-5-en-3ß,17α-diol (1), 3-O-ß-D-glucopyranosyl(1â4)-ß-D- fucopyranosyl-(25S)-spirost-5-en-3ß,17α-diol (2), 3-O-ß-D-glucopyranosyl(1â2) -ß-D-glucopyranosyl(1â4)-ß-D-fucopyranosyl-(25R)-spirost-5-en-3ß,17α-diol (3), 3-O-ß-D-glucopyranosyl(1â4)-ß-D-fucopyranosyl-(25R/S)-spirost-5-en-3ß,12ß-diol (4), together with five known steroidal saponins were isolated from the ethanolic extract of the rhizome of Polygonatum sibiricum. Chemical structures of these compounds were elucidated by spectroscopic techniques. Anti-inflammatory activities of these new compounds were evaluated.
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Polygonatum/química , Rizoma/química , Saponinas/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Fitosteroles/químicaRESUMEN
BACKGROUND: Previous studies indicated that both red blood cell distribution width (RDW) and neutrophil to lymphocyte ratio (NLR) were useful indices in assessing the disease activity of autoimmune diseases. However, the evidence for the association between RDW, NLR and dermatomyositis (DM) and polymyositis (PM) is limited. The aim of this study is to investigate the association between the disease activity of PM/DM and both RDW and NLR. METHODS: Medical records of 114 PM/DM patients and 114 healthy controls were retrospectively reviewed, and their RDW, NLR and myositis disease activity assessment visual analogue scale (MYOACT) on admission were extracted. The correlations between RDW, NLR and MYOACT were analyzed using the Spearman approach and multivariable model. RESULTS: PM/DM patients had significantly higher RDW and NLR. Increased RDW in PM/DM patients was not completely attributed to decreased hemoglobin or therapeutic agents. Both RDW and NLR are independently and positively correlated MYOACT. CONCLUSION: Both RDW and NLR are useful indices in assessing the disease activity of PM/DM.
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Dermatomiositis , Índices de Eritrocitos/fisiología , Recuento de Leucocitos/estadística & datos numéricos , Linfocitos/citología , Neutrófilos/citología , Polimiositis , Adulto , Estudios de Casos y Controles , Dermatomiositis/sangre , Dermatomiositis/epidemiología , Dermatomiositis/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimiositis/sangre , Polimiositis/epidemiología , Polimiositis/fisiopatologíaRESUMEN
BACKGROUND/AIMS: Coronary microembolization (CME) can lead to no-reflow or slow reflow, which is one of the important reasons for loss of clinical benefit from myocardial reperfusion therapy. MicroRNAs and autophagy are heavily implicated in the occurrence and development of almost all cardiovascular diseases. Therefore, the present study was designed to investigate the role of miR-30e-3p and autophagy in CME-induced myocardial injury rat model. METHODS: Sixty rats were randomly divided into six groups: sham, CME 1h,3h,6h,9h, and 12h (n = 10 per group). Our CME rat model was created by injecting polyethylene microspheres (42mm) into the left ventricle of the heart; the sham group was injected with same volume of normal saline. The cardiac function and serum cardiac troponin I (cTnI) level of each group was measured. HE staining and HBFP staining were used to evaluate the myocardial micro-infarction area of myocardium tissue samples. Then RT-qPCR and western blot were used to detect the expression of miR-30e-3p and, autophagy related protein LC3-II and p62, respectively. Transmission electron microscope (TEM) was used to identify autophagic vacuoles in tissue samples. RESULTS: The cardiac function of the CME 6h,9h, and 12h groups were significantly decreased compared to the sham group (P < 0.05) and the cTnI level in each group were also significantly increased (P < 0.05). The expression of miR-30e-3p in the CME 6h, 9h and 12h group were decreased significantly compared with the sham group (P < 0.05). Meanwhile, the expression of autophagy related protein LC3-II decreased significantly and p62 increased significantly in the CME 9h and 12h group (P < 0.05). TEM images showed typical autophagic vacuoles for each of the CME groups. CONCLUSIONS: Myocardial miR-30e-3p is down regulated after CME and is accompanied by inhibited autophagy and decreased cardiac function. Therefore, miR-30e-3p may be involved in CME-induced cardiac dysfunction by regulating myocardial autophagy.
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Autofagia , Embolia/patología , Lesiones Cardíacas/etiología , MicroARNs/metabolismo , Animales , Vasos Coronarios/lesiones , Vasos Coronarios/patología , Modelos Animales de Enfermedad , Regulación hacia Abajo , Ecocardiografía , Embolia/complicaciones , Lesiones Cardíacas/metabolismo , Lesiones Cardíacas/patología , Ventrículos Cardíacos/fisiopatología , Masculino , MicroARNs/genética , Microscopía Electrónica de Transmisión , Microesferas , Proteínas Asociadas a Microtúbulos/metabolismo , Miocardio/metabolismo , Miocardio/patología , Polietileno/toxicidad , Ratas , Ratas Sprague-Dawley , Proteína Sequestosoma-1/metabolismo , Troponina I/sangre , Regulación hacia ArribaRESUMEN
Cell membrane chromatography is a useful tool for screening active compounds from natural products. As the reason of separation mechanism, traditional cell membrane chromatography could not be used for screening the active compounds absorbed through the cell membrane and influencing the cell signal transduction pathway. In this work, we establish a new method named cell extraction combined with off-line HPLC for screening the compounds penetrating the cell membrane. This is the first time 3 T3-L1 adipocyte culture has been combined with HPLC technology. Compared with other cell membrane chromatography methods, there is good resolution and no further analysis by other chromatographic steps is required. On co-incubating crude extracts of Coptis chinensis with cells and analyzing the compounds extracted by the cells, active compounds such as berberine were detected. Glucose consumption tests showed that berberine could increase glucose consumption by insulin-resistant 3 T3-L1 adipocytes. The levels of intracellular berberine correlated with its activity. The results indicate that the developed method could be an alternative method for screening active compounds from natural products.
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Adipocitos/metabolismo , Membrana Celular/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Coptis/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Animales , Berberina/análisis , Berberina/metabolismo , Berberina/farmacología , Membrana Celular/efectos de los fármacos , Coptis/metabolismo , Evaluación Preclínica de Medicamentos , Glucosa/metabolismo , Ratones , Extractos Vegetales/metabolismoRESUMEN
OBJECTIVE: AGEs induce endothelial cell dysfunction in HUVECs, resulting in ROS production and triggering apoptosis. This study sought to identify miRNAs involved in AGE-induced endothelial cell injury. METHODS: Microarray analysis to identify miRNAs altered with AGE stimulation was undertaken, and results were confirmed using real-time quantitative polymerase chain reaction. The interaction of miRNAs with the RhoA and ROCK2 genes was confirmed using luciferase assays, and their effects on expression were determined using Western blot analysis. The effects of AGEs and miRNAs on endothelial cell permeability were assessed. RESULTS: AGEs induced ROS production and apoptosis of HUVECs (p < 0.05). AGE-induced miR-200b and miR-200c downregulation led to increased expression of their target genes, RhoA and ROCK, respectively. AGE-induced endothelial cell permeability and F-actin expression were significantly reduced with both miR-200b and miR-200c mimics (p < 0.05). Furthermore, AGE-induced stress fiber formation was reduced in cells treated with miR-200b mimics. CONCLUSION: miR-200b and miR-200c are suppressed in AGE-induced endothelial cell injury, resulting in unregulated RhoA/ROCK2 signaling. Further studies are necessary to evaluate the therapeutic value of targeting miRNAs or their target genes for treatment of vascular diseases.
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Permeabilidad Capilar , Productos Finales de Glicación Avanzada/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , MicroARNs/metabolismo , Quinasas Asociadas a rho/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Apoptosis/efectos de los fármacos , Productos Finales de Glicación Avanzada/farmacología , Células Endoteliales de la Vena Umbilical Humana/patología , HumanosRESUMEN
Objective: Adverse events associated with dexmedetomidine were analyzed using data from the FDA's FAERS database, spanning from 2004 to the third quarter of 2023. This analysis serves as a foundation for monitoring dexmedetomidine's safety in clinical applications. Methods: Data on adverse events associated with dexmedetomidine were standardized and analyzed to identify clinical adverse events closely linked to its use. This analysis employed various signal quantification analysis algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS). Results: In the FAERS database, dexmedetomidine was identified as the primary suspect in 1,910 adverse events. Our analysis encompassed 26 organ system levels, from which we selected 346 relevant Preferred Terms (PTs) for further examination. Notably, adverse drug reactions such as diabetes insipidus, abnormal transcranial electrical motor evoked potential monitoring, acute motor axonal neuropathy, and trigeminal cardiac reflex were identified. These reactions are not explicitly mentioned in the drug's specification, indicating the emergence of new signals for adverse drug reactions. Conclusion: Data mining in the FAERS database has elucidated the characteristics of dexmedetomidine-related adverse drug reactions. This analysis enhances our understanding of dexmedetomidine's drug safety, aids in the clinical management of pharmacovigilance studies, and offers valuable insights for refining drug-use protocols.
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OBJECTIVE: Both depression and insomnia are found to be more prevalent in cancer patients compared to the general population. This study compared the network structures of depression and insomnia among cancer patients versus cancer-free participants (controls hereafter). METHOD: The 8-item Center for Epidemiological Studies Depression Scale (CESD-8) and the 4-item Jenkins Sleep Scale (JSS-4) were used to measure depressive and insomnia symptoms, respectively. Propensity score matching (PSM) was used to construct the control group using data from the Health and Retirement Study (HRS). In total, a sample consisting of 2216 cancer patients and 2216 controls was constructed. Central (influential) and bridge symptoms were estimated using the expected influence (EI) and bridge expected influence (bridge EI), respectively. Network stability was assessed using the case-dropping bootstrap method. RESULT: The prevalence of depression (CESD-8 total score ≥ 4) in cancer patients was significantly higher compared to the control group (28.56 % vs. 24.73 %; P = 0.004). Cancer patients also had more severe depressive symptoms relative to controls, but there was no significant group difference for insomnia symptoms. The network structures of depressive and insomnia symptoms were comparable between cancer patients and controls. "Felt sadness" (EI: 6.866 in cancer patients; EI: 5.861 in controls), "Felt unhappy" (EI: 6.371 in cancer patients; EI: 5.720 in controls) and "Felt depressed" (EI: 6.003 in cancer patients; EI: 5.880 in controls) emerged as the key central symptoms, and "Felt tired in morning" (bridge EI: 1.870 in cancer patients; EI: 1.266 in controls) and "Everything was an effort" (bridge EI: 1.046 in cancer patients; EI: 0.921 in controls) were the key bridge symptoms across both groups. CONCLUSION: Although cancer patients had more frequent and severe depressive symptoms compared to controls, no significant difference was observed in the network structure or strength of the depressive and insomnia symptoms. Consequently, psychosocial interventions for treating depression and insomnia in the general population could be equally applicable for cancer patients who experience depression and insomnia.
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Depresión , Neoplasias , Puntaje de Propensión , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Masculino , Femenino , Neoplasias/complicaciones , Neoplasias/psicología , Neoplasias/epidemiología , Depresión/epidemiología , Persona de Mediana Edad , Anciano , Prevalencia , Escalas de Valoración Psiquiátrica , Estudios de Casos y Controles , Jubilación/psicologíaRESUMEN
Importance: Postpartum depression (PPD) is one of the most common mental health conditions during the perinatal and postpartum periods, which can have adverse effects on both mother and infant. Objective: To investigate the efficacy of perioperative adjunctive esketamine administration after cesarean deliveries in the prevention of PPD. Design, Setting, and Participants: A single-center, double-blind, placebo-controlled, randomized clinical trial was conducted from January 1, 2022, to January 1, 2023, at Fujian Provincial Hospital among 298 women aged 18 to 40 years, with an American Society of Anesthesiologists grade I to III classification and singleton full-term pregnancies who were scheduled for elective cesarean deliveries. Primary analyses were performed on a modified intention-to-treat basis. Interventions: Patients were randomly assigned to the esketamine (n = 148) and control (n = 150) groups. Those in the esketamine group received a single intravenous injection of 0.25 mg/kg of esketamine immediately after fetal delivery, followed by 50 mg of esketamine as an adjuvant in patient-controlled intravenous analgesia for 48 hours after surgery. Saline was given to the control group of patients. Main Outcomes and Measures: The primary outcome was assessments of PPD symptoms by using the Edinburgh Postnatal Depression Scale (EPDS) at postpartum day 7. Positive screening for PPD was defined as a score of 10 or more points on the EPDS. In addition, the EPDS was analyzed as a continuous variable to evaluate depressive symptoms. Secondary outcomes included the Numeric Rating Scale (NRS) of postoperative pain, along with safety evaluations including adverse events and clinical assessments at postpartum days 14, 28, and 42. Results: A total of 298 pregnant women were included, with 150 in the control group (median age, 31.0 years [IQR, 29.0-34.0 years]) and 148 in the esketamine group (median age, 31.0 years [IQR, 28.0-34.0 years]). The prevalence of depression symptoms was significantly lower among patients given esketamine compared with controls (23.0% [34 of 148] vs 35.3% [53 of 150]; odds ratio, 0.55; 95% CI, 0.33-0.91; P = .02) on postpartum day 7. In addition, the esketamine group also showed a significantly lower change in EPDS scores (difference of least-squares means [SE], -1.17 [0.44]; 95% CI, -2.04 to -0.31; effect size, 0.74; P = .008). However, there were no differences between the groups in the incidence of positive screening results for PPD or in changes from the baseline EPDS scores at postpartum days 14, 28, and 42. There were no differences in NRS scores at rest and on movement except on movement at 72 hours postoperatively, when scores were significantly lower in the esketamine group (median, 3.0 [IQR, 2.0-3.0] vs 3.0 [IQR, 3.0-3.5]; median difference, 0 [95% CI, 0-0]; P = .03). Conclusions and Relevance: These results suggest that intravenous administration of esketamine during the perioperative period of elective cesarean delivery can improve depression symptoms during the early postpartum period. However, this antidepression effect may not be universally applicable to patients with low EPDS scores. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100054199.
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Depresión Posparto , Ketamina , Adulto , Femenino , Humanos , Embarazo , Adyuvantes Inmunológicos , Cesárea , Depresión Posparto/epidemiología , Depresión Posparto/prevención & control , Ketamina/uso terapéutico , Adolescente , Adulto JovenRESUMEN
Inositol hexaphosphate (InsP6) is the major storage form of phosphorus in seeds. Reducing seed InsP6 content is a breeding objective in agriculture, as InsP6 negatively impacts animal nutrition and the environment. Nevertheless, how InsP6 accumulation is regulated remains largely unknown. Here, we identify a clade of receptor-like cytoplasmic kinases (RLCKs), named Inositol Polyphosphate-related Cytoplasmic Kinases 1-6 (IPCK1-IPCK6), deeply involved in InsP6 accumulation. The InsP6 concentration is dramatically reduced in seeds of ipck quadruple (T-4m/C-4m) and quintuple (C-5m) mutants, accompanied with the obviously increase of phosphate (Pi) concentration. The plasma membrane-localized IPCKs recruit IPK1 involved in InsP6 synthesis, and facilitate its binding and activity via phosphorylation of GRF 14-3-3 proteins. IPCKs also recruit IPK2s and PI-PLCs required for InsP4/InsP5 and InsP3 biosynthesis respectively, to form a potential IPCK-GRF-PLC-IPK2-IPK1 complex. Our findings therefore uncover a regulatory mechanism of InsP6 accumulation governed by IPCKs, shedding light on the mechanisms of InsP biosynthesis in eukaryotes.
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Proteínas 14-3-3 , Proteínas de Arabidopsis , Arabidopsis , Ácido Fítico , Proteínas 14-3-3/metabolismo , Proteínas 14-3-3/genética , Ácido Fítico/metabolismo , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Fosforilación , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Mutación , Membrana Celular/metabolismo , Regulación de la Expresión Génica de las Plantas , Fosfatos de Inositol/metabolismoRESUMEN
Purpose: Sleep disorders are common globally. Probiotics may improve human microbial diversity, offering potential benefits for sleep disturbances by enhancing sleep quality and reducing disorders. We aimed to use a population-based study to investigate the association between yogurt (a probiotic food) and probiotic consumption with sleep disturbances in US adults. Methods: A total of 49,693 adults from the 2009-2018 National Health and Nutrition Examination Survey (NHANES) were included in the analyses. Sleep disorders and sleep duration were assessed according to the Sleep Disorders Questionnaire. The Dietary Questionnaire evaluated yogurt and dietary supplements containing probiotic consumption. After adjusting for confounding factors, weighted multivariable logistic regression and subgroup analyses were used to assess the association between yogurt and probiotic consumption and sleep status. Results: Of the study cohort, 3535 (14.24 %) participants consumed yogurt and/or dietary supplements containing probiotics. The prevalence of sleep disorders was 16.22 %. Only 53.51 % of the participants achieved the recommended amount of sleep (7-9 h), with 6.10 % and 33.48 % having excessive and insufficient sleep duration, respectively. Weighted Logistic regression models indicated a significant association of probiotic intake with a decreased risk of sleep disturbances compared with those without yogurt or probiotic consumption after adjustments. (For sleep disorders: OR: 0.96, 95 % CI 0.94-0.98, P < 0.001; for sleep duration: OR: 0.98, 95 % CI 0.96-1.00, P = 0.081) Moreover, the effect size of the probiotic intake on sleep was especially significant in sex, race, and BMI subgroups. Conclusion: The present study first indicated that yogurt and probiotic consumption were associated with a reduced risk of sleep disturbances in US adults, particularly among males, whites, and those with a normal BMI. Incorporating yogurt or probiotics into the diet could serve as a public health strategy for improving sleep disturbances, though further investigation into the underlying mechanisms is needed.
RESUMEN
Transforming growth factor-ß (TGF-ß) protein has been supposed to be a risk factor for liver cirrhosis; however, the associations between its genes (TGF-ß -509C>T and +869T>C) and liver cirrhosis remained unclear. This study was to quantitatively analyze the correlations by using a meta-analysis. Pubmed, Embase, Wanfang databases were retrieved up to November 1st, 2011. Odds ratio (OR) and 95 % confidence interval (95 %CI) were used to demonstrate the strength of association, and P < 0.05 of Z test indicated statistical significance. Combined analyses were performed by using fixed or random-effect model, depending on between-study heterogeneity. Seven studies were for TGF-ß -509C>T polymorphism, and eight studies were for +869T>C polymorphism. Combined results indicated that neither TGF-ß -509C>T nor +869T>C polymorphisms were associated with risk of liver cirrhosis [OR (95 % CI): 0.79 (0.60-1.04) for CT vs. TT of -509C>T and 0.87 (0.68-1.12) for CT vs. CC of +869T>C], with no between-study heterogeneity. In addition, subgroups analyses still inferred that two polymorphisms were not associated with risk of liver cirrhosis for HBV-infected patients, Asians and for Population-based studies. This meta-analysis indicated that neither TGF-ß -509C>T nor +869T>C polymorphisms were associated with risk of liver cirrhosis, regardless of HBV infection or not.
Asunto(s)
Cirrosis Hepática/genética , Polimorfismo de Nucleótido Simple , Factor de Crecimiento Transformador beta/genética , Alelos , Estudios de Casos y Controles , Heterogeneidad Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Oportunidad Relativa , Sesgo de PublicaciónRESUMEN
BACKGROUND: Statins are widely prescribed to reduce cholesterol levels in the prevention of atherosclerotic cardiovascular disease. However, the debate about the effect of statins on cancer risk remains unsettled. The aim of this study was to investigate the association of utilization of statins with the risk of gastric cancer by carrying out a meta-analysis. METHODS: A literature search was performed on PubMed and EMBASE up to March 2013 to identify the cohort or case-control studies or randomized controlled trials (RCTs) that examined the relationship between statins use and the risk of gastric cancer. The bibliographies of the retrieved articles were also reviewed to identify additional studies. A random-effects model was used to calculate the summary relative risks (RRs) with 95 % confidence intervals (CIs). RESULTS: Three post-hoc analyses of 26 RCTs involving 290 gastric cancers and eight observational studies totaling 7,321 gastric cancers were included. Statins use was shown to be significantly associated with a 27 % reduction in the risk of gastric cancer (RR = 0.73, 95 % CI = 0.58-0.93), with considerable heterogeneity among studies (I (2) = 88.9 %). Excluding one study in which all subjects are diabetic patients obtained an attenuated, but homogeneous result (RR = 0.85, 95 % CI = 0.80-0.91, I (2) = 0.0 %). These findings were consistent in the subgroup analysis. CONCLUSION: A meta-analysis of existing evidence, primarily from observational studies, indicates that use of statins reduces the risk of gastric cancer.
Asunto(s)
Utilización de Medicamentos/tendencias , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Neoplasias Gástricas/prevención & control , Utilización de Medicamentos/estadística & datos numéricos , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Gástricas/epidemiologíaRESUMEN
BACKGROUND: The lung microbiome plays a crucial role in human health and disease. Extensive studies have demonstrated that the disturbance of the lung microbiome influences immune response, cognition, and behavior. The goal of this study was to investigate the effect of general anesthetics on lung microbiome. METHODS: Eight-week-old male SD rats received a continuous intravenous infusion of propofol or inhalation of isoflurane for 4 h. 16S rRNA gene amplification from BALF samples was used to investigate the changes in the lung microbiome after interventions. We further performed neurobehavioral assessments to find the differential strains' association with behavior disorder after isoflurane anesthesia. RESULTS: The absolute and relative quantitation of 16S rRNA sequencing data showed that isoflurane altered the diversity and abundance of the lung microbiome in rats more than propofol. Elusimicrobia increased significantly in the isoflurane group. Both EPM and OFT results showed that rats exhibited depression-like behaviors after inhalation of isoflurane. In addition, significant differences were found in the COG/KO/MetaCyc/KEGG pathway enrichment analyses among the groups. CONCLUSION: Continuous inhalation of isoflurane changed the diversity and composition of the lung microbiota in rats, resulting in post-anesthesia depression.