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Both copper (Cu) excess and boron (B) deficiency are often observed in some citrus orchard soils. The molecular mechanisms by which B alleviates excessive Cu in citrus are poorly understood. Seedlings of sweet orange (Citrus sinensis (L.) Osbeck cv. Xuegan) were treated with 0.5 (Cu0.5) or 350 (Cu350 or Cu excess) µM CuCl2 and 2.5 (B2.5) or 25 (B25) µM HBO3 for 24 weeks. Thereafter, this study examined the effects of Cu and B treatments on gene expression levels revealed by RNA-Seq, metabolite profiles revealed by a widely targeted metabolome, and related physiological parameters in leaves. Cu350 upregulated 564 genes and 170 metabolites, and downregulated 598 genes and 58 metabolites in leaves of 2.5 µM B-treated seedlings (LB2.5), but it only upregulated 281 genes and 100 metabolites, and downregulated 136 genes and 40 metabolites in leaves of 25 µM B-treated seedlings (LB25). Cu350 decreased the concentrations of sucrose and total soluble sugars, and increased the concentrations of starch, glucose, fructose, and total nonstructural carbohydrates (TNC) in LB2.5, but it only increased the glucose concentration in LB25. Further analysis demonstrated that B addition reduced the oxidative damage and alterations in primary and secondary metabolisms caused by Cu350; and alleviated the impairment of Cu350 to photosynthesis and cell wall metabolism, thus improving leaf growth. LB2.5 exhibited some adaptive responses to Cu350 to meet the increasing need for the dissipation of excessive excitation energy (EEE) and the detoxification of reactive oxygen species (reactive aldehydes) and Cu. Cu350 increased photorespiration, xanthophyll cycle-dependent thermal dissipation, nonstructural carbohydrate accumulation, and secondary metabolite biosynthesis and abundances; and upregulated tryptophan metabolism and related metabolite abundances, and some antioxidant-related gene expression, and some antioxidant abundances. Additionally, this study identified some metabolic pathways, metabolites, and genes that might lead to Cu tolerance in leaves.
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BACKGROUND: Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear. METHODS: We combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays. RESULTS: We identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells. CONCLUSIONS: We identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.
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Fibroblastos Asociados al Cáncer , Carcinoma Hepatocelular , Neoplasias Hepáticas , Células Madre Neoplásicas , Microambiente Tumoral , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Microambiente Tumoral/genética , Proteómica/métodos , Transcriptoma , Regulación Neoplásica de la Expresión Génica , Genómica/métodos , Proliferación Celular , Perfilación de la Expresión Génica , Línea Celular Tumoral , Pronóstico , MultiómicaRESUMEN
OBJECTIVE: To compare the haemodynamic effects of different ankle movements combined ankle and toe movements on the femoral vein of the lower extremity. METHODS: 28 healthy volunteers participated in the study. Doppler ultrasound was used to measure peak systolic velocity and time-averaged mean velocity of the common femoral vein during ankle dorsiflexion, ankle dorsiflexion with simultaneous toe extension, ankle plantarflexion, and ankle plantarflexion with simultaneous toe flexion. RESULTS: In comparison to the resting state, both ankle alone or ankle combined with toe movement showed statistically significant differences (p < .01). However, there were no significant difference in the velocity of the common femoral vein between ankle alone and ankle combined with toe movement (p > .05). It is noteworthy that dorsiflexion of the ankle resulted in the highest peak velocity of blood flow. CONCLUSION: The impact of ankle movement, with or without toe movement, the velocity of the common femoral vein is not significantly correlated.
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BACKGROUND: Clinical blood resources are scarce and autologous blood transfusion for extracorporeal membrane oxygenation (ECMO) withdrawal is less studied. OBJECTIVES: To assess the use of staged autotransfusion during ECMO decannulation. METHODS: The study included ECMO withdrawal patients. Patients in the autologous transfusion group underwent staged transfusion during ECMO withdrawal, while those in the control group received 2.0 units of allogeneic packed red blood cells (RBCs) to increase hemoglobin (Hb). Parameters such as Hb, hematocrit (Hct), adverse events, decannulation success rate, volume of allogeneic RBC transfusions, and transfusion costs were compared. RESULTS: A total of 82 Chinese patients were enrolled, with a mean age of 46 years, 27 were female, and the top three primary diagnoses were cardiac arrest, acute myocarditis, and severe pneumonia. There were 41 individuals in the autologous blood transfusion group and 41 in the control group. No significant differences were observed in Hb, Hct, adverse events, and the success rate for decannulation between the two groups (all P > 0.05). Compared with the control group, the volume of allogeneic RBC transfusions [0 (0â¼1.50) U vs. 3.5 (1.88â¼40) U, P < 0.001] and the total cost [130 (130â¼390) Chinese Yuan (CNY) vs. 910 (487.50, 1040) CNY, P = 0.002] were lower in the autologous transfusion group. CONCLUSION: In comparison with allogeneic RBC transfusion, staged autotransfusion during ECMO decannulation not only effectively maintained Hb levels but also reduced the requirement for allogeneic RBC transfusions. In addition, this approach decreased the associated costs and did not increase the risk of clinical adverse events.
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BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is used for severe cardiopulmonary failure, with veno-arterial ECMO for cardiogenic shock and veno-venous ECMO for acute respiratory failure. ECMO's application has expanded to ICUs, emergency departments, and operating rooms. ECMO patients are at high risk for complications, including acute kidney injury (AKI), often requiring renal replacement therapy (RRT), posing significant management challenges. METHODS: From August 2015 to June 2022, 120 patients were cured with veno-venous ECMO (nâ =â 60) or veno-arterial ECMO (VA-ECMO, nâ =â 60) combined with CRRT in our hospital. In the control group (nâ =â 60), the input end (arterial end) of CRRT was connected to the ECMO oxygenator. The reinfusion end (venous end) of CRRT was connected to the oxygenator of ECMO for CRRTâ +â ECMO treatment. In the experimental group (nâ =â 60), the input end (arterial end) of CRRT was connected to the oxygenator of ECMO, and an additional pressure regulating device was installed on the connection of the 2 lines. The observation indexes including clinical therapeutic effect, clinical therapeutic effect, the incidence of complications, and the incidence of complications were compared. RESULTS: There was a notable decrease in serum creatinine, and the differences in blood urea nitrogen, procalcitonin, and C-reactive protein after operation were statistically significant (Pâ <â .05). The filter use time in the study group was notably longer (Pâ <â .01). There exhibited no remarkable difference in the incidences of bleeding, thrombosis, numbness of hands and feet, metabolic alkalosis, disseminated intravascular coagulation, organ dysfunction syndrome, hyperbilirubinemia, and infection. CONCLUSION: This study demonstrates that additional pressure regulation devices are installed at the line connection between the CRRT input end and the CRRT return end to ensure that the flow rate of ECMO does not affect the CRRT treatment. ECMO and CRRT provide a safe pressure range so that the ECMO line can be safely connected to the CRRT machine at physiological pressure, reducing the occurrence of complications related to CRRT machine interruption and improving the efficiency of CRRT without affecting the efficiency of ECMO, ensuring patient safety.
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Lesión Renal Aguda , Oxigenación por Membrana Extracorpórea , Terapia de Reemplazo Renal , Humanos , Oxigenación por Membrana Extracorpórea/métodos , Oxigenación por Membrana Extracorpórea/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Lesión Renal Aguda/terapia , Terapia de Reemplazo Renal/métodos , Anciano , Incidencia , AdultoRESUMEN
Numerous research works have investigated the potential impact of endocrine hormones on the severity of COVID-19-related pneumonia in individuals. However, there are few studies on the effect of pre-onset neuroendocrine hormones on the prognosis of COVID-19 patients. This study looked into the prognostic value of pre-onset hair hormone levels in COVID-19 infected individuals. This study included 27 patients with COVID-19 and collected patient information and laboratory indicators. The hormone levels in hair were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Within 28 days, 63 % of the patients in this study passed away. With 28-day mortality as the outcome index, urea nitrogen, CURB-65 score and pneumonia severity score (PSI) of 2 groups were statistically significant (P < 0.05). Among all hormone levels detected in hair, only progesterone level was substantially correlated negatively with COVID-19 patients' 28-day mortality(P < 0.05). The level of progesterone in hair was substantially adversely connected with the death rate at 28 days of COVID-19 patients, according to correlation and logistic regression analysis(P < 0.05). Among patients with COVID-19 pneumonia, hair progesterone levels were strongly associated with 28-day mortality, which emphasizes hair progesterone's importance as a prognostic factor.
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Accurately identifying life-threatening prostate cancer (PCa) at time of diagnosis remains an unsolved problem. We evaluated whether DNA methylation status of selected candidate genes can predict the risk of metastasis beyond clinical risk factors in men with untreated PCa. A nested case-control study was conducted among men diagnosed with localized PCa at Kaiser Permanente California between 01/01/1997-12/31/2006 who did not receive curative treatments. Cases were those who developed metastasis within 10 years from diagnosis. Controls were selected using density sampling. Ninety-eight candidate genes were selected from functional categories of cell cycle control, metastasis/tumour suppressors, cell signalling, cell adhesion/motility/invasion, angiogenesis, and immune function, and 41 from pluripotency genes. Cancer DNA from diagnostic biopsy blocks were extracted and analysed. Associations of methylation status were assessed using CpG site level and principal components-based analysis in conditional logistic regressions. In 215 cases and 404 controls, 27 candidate genes were found to be statistically significant in at least one of the two analytical approaches. The agreement between the methods was 25.9% (7 candidate genes, including 2 pluripotency markers). The DNA methylation status of several candidate genes was significantly associated with risk of metastasis in untreated localized PCa patients. These findings may inform future risk prediction models for PCa metastasis beyond clinical characteristics.
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Metilación de ADN , Neoplasias de la Próstata , Masculino , Humanos , Estudios de Casos y Controles , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Factores de RiesgoRESUMEN
Citrus is mainly cultivated in acid soil with low boron (B) and high copper (Cu). In this study, Citrus sinensis seedlings were submitted to 0.5 (control) or 350 µM Cu (Cu excess or Cu exposure) and 2.5, 10, or 25 µM B for 24 weeks. Thereafter, H2O2 production rate (HPR), superoxide production rate (SAPR), malondialdehyde, methylglyoxal, and reactive oxygen species (ROS) and methylglyoxal detoxification systems were measured in leaves and roots in order to test the hypothesis that B addition mitigated Cu excess-induced oxidative damage in leaves and roots by reducing the Cu excess-induced formation and accumulation of ROS and MG and by counteracting the impairments of Cu excess on ROS and methylglyoxal detoxification systems. Cu and B treatments displayed an interactive influence on ROS and methylglyoxal formation and their detoxification systems. Cu excess increased the HPR, SAPR, methylglyoxal level, and malondialdehyde level by 10.9% (54.3%), 38.9% (31.4%), 50.3% (24.9%), and 312.4% (585.4%), respectively, in leaves (roots) of 2.5 µM B-treated seedlings, while it only increased the malondialdehyde level by 48.5% (97.8%) in leaves (roots) of 25 µM B-treated seedlings. Additionally, B addition counteracted the impairments of Cu excess on antioxidant enzymes, ascorbate-glutathione cycle, sulfur metabolism-related enzymes, sulfur-containing compounds, and methylglyoxal detoxification system, thereby protecting the leaves and roots of Cu-exposed seedlings against oxidative damage via the coordinated actions of ROS and methylglyoxal removal systems. Our findings corroborated the hypothesis that B addition alleviated Cu excess-induced oxidative damage in leaves and roots by decreasing the Cu excess-induced formation and accumulation of ROS and MG and by lessening the impairments of Cu excess on their detoxification systems. Further analysis indicated that the pathways involved in the B-induced amelioration of oxidative stress caused by Cu excess differed between leaves and roots.
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The MHC-I antigen presentation (AP) pathway is key to shaping mammalian CD8+ T cell immunity, with its aberrant expression closely linked to low tumor immunogenicity and immunotherapy resistance. While significant attention has been given to genetic mutations and downregulation of positive regulators that are essential for MHC-I AP, there is a growing interest in understanding how tumors actively evade MHC-I expression and/or AP through the induction of MHC-I inhibitory pathways. This emerging field of study may offer more viable therapeutic targets for future cancer immunotherapy. Here, we explore potential mechanisms by which cancer cells evade MHC-I AP and function and propose therapeutic strategies that might target these MHC-I inhibitors to restore impaired T cell immunity within the tumor microenvironment (TME).
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Antígenos de Histocompatibilidad Clase I , Neoplasias , Animales , Humanos , Antígenos de Histocompatibilidad Clase I/metabolismo , Linfocitos T CD8-positivos , Inmunoterapia , Antígenos de Neoplasias , Mamíferos , Microambiente TumoralRESUMEN
Both anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) originate from thyroid follicular epithelial cells, but ATC has a significantly worse prognosis and shows resistance to conventional therapies. However, clinical trials found that immunotherapy works better in ATC than late-stage PTC. Here, we used single-cell RNA sequencing (scRNA-Seq) to generate a single-cell atlas of thyroid cancer. Differences in ATC and PTC tumor microenvironment components (including malignant cells, stromal cells, and immune cells) leading to the polarized prognoses were identified. Intriguingly, we found that CXCL13+ T lymphocytes were enriched in ATC samples and might promote the development of early tertiary lymphoid structure (TLS). Last, murine experiments and scRNA-Seq analysis of a treated patient's tumor demonstrated that famitinib plus anti-PD-1 antibody could advance TLS in thyroid cancer. We displayed the cellular landscape of ATC and PTC, finding that CXCL13+ T cells and early TLS might make ATC more sensitive to immunotherapy.
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Quimiocina CXCL13 , Inmunoterapia , Cáncer Papilar Tiroideo , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Microambiente Tumoral , Microambiente Tumoral/inmunología , Humanos , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/terapia , Carcinoma Anaplásico de Tiroides/inmunología , Animales , Ratones , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/inmunología , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/terapia , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/inmunología , Neoplasias de la Tiroides/terapia , Neoplasias de la Tiroides/genética , Inmunoterapia/métodos , Quimiocina CXCL13/metabolismo , Quimiocina CXCL13/genética , Estructuras Linfoides Terciarias/inmunología , Estructuras Linfoides Terciarias/patología , Análisis de la Célula Individual , Pronóstico , Linfocitos T/inmunología , Femenino , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , MasculinoRESUMEN
Pathological pain emerges from nociceptive system dysfunction, resulting in heightened pain circuit activity. Various forms of circuitry plasticity, such as central sensitization, synaptic plasticity, homeostatic plasticity, and excitation/inhibition balance, contribute to the malfunction of neural circuits during pain pathogenesis. Recently, a new form of plasticity in the spinal dorsal horn (SDH), named neural circuit polarization (NCP), was discovered in pain models induced by HIV-1 gp120 and chronic morphine administration. NCP manifests as an increase in excitatory postsynaptic currents (EPSCs) in excitatory neurons and a decrease in EPSCs in inhibitory neurons, presumably facilitating hyperactivation of pain circuits. The expression of NCP is associated with astrogliosis. Ablation of reactive astrocytes or suppression of astrogliosis blocks NCP and, concomitantly, the development of gp120- or morphine-induced pain. In this review, we aim to compare and integrate NCP with other forms of plasticity in pain circuits to improve the understanding of the pathogenic contribution of NCP and its cooperation with other forms of circuitry plasticity during the development of pathological pain.
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Gliosis , Células del Asta Posterior , Humanos , Gliosis/metabolismo , Células del Asta Posterior/metabolismo , Dolor/metabolismo , Asta Dorsal de la Médula Espinal , Derivados de la Morfina/metabolismoRESUMEN
Little information is available on how boron (B) supplementation affects plant cell wall (CW) remodeling under copper (Cu) excess. 'Xuegan' (Citrus sinensis) seedlings were submitted to 0.5 or 350 µM Cu × 2.5 or 25 µM B for 24 weeks. Thereafter, we determined the concentrations of CW materials (CWMs) and CW components (CWCs), the degree of pectin methylation (DPM), and the pectin methylesterase (PME) activities and PME gene expression levels in leaves and roots, as well as the Cu concentrations in leaves and roots and their CWMs (CWCs). Additionally, we analyzed the Fourier transform infrared (FTIR) and X-ray diffraction (XRD) spectra of leaf and root CWMs. Our findings suggested that adding B reduced the impairment of Cu excess to CWs by reducing the Cu concentrations in leaves and roots and their CWMs and maintaining the stability of CWs, thereby improving leaf and root growth. Cu excess increased the Cu fractions in leaf and root pectin by decreasing DPM due to increased PME activities, thereby contributing to citrus Cu tolerance. FTIR and XRD indicated that the functional groups of the CW pectin, hemicellulose, cellulose, and lignin could bind and immobilize Cu, thereby reducing Cu cytotoxicity in leaves and roots.
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Citrus sinensis , Boro/toxicidad , Cobre/toxicidad , Plantones , Pared Celular , Hojas de la Planta , Pectinas/farmacologíaRESUMEN
BACKGROUND: Autophagic defects are involved in Methamphetamine (Meth)-induced neurotoxicity. Syntaxin 17 (Stx17), a member of the SNARE protein family, participating in several stages of autophagy, including autophagosome-late endosome/lysosome fusion. However, the role of Stx17 and potential mechanisms in autophagic defects induced by Meth remain poorly understood. METHODS: To address the mechanism of Meth-induced cognitive impairment, the adenovirus (AV) and adeno-associated virus (AAV) were injected into the hippocampus for stereotaxis to overexpress Stx17 in vivo to examine the cognitive ability via morris water maze and novel object recognition. In molecular level, the synaptic injury and autophagic defects were evaluated. To address the Meth induced neuronal damage, the epidermal growth factor receptor (EGFR) degradation assay was performed to evaluate the degradability of the "cargos" mediated by Meth, and mechanistically, the maturation of the vesicles, including autophagosomes and endosomes, were validated by the Co-IP and the GTP-agarose affinity isolation assays. RESULTS: Overexpression of Stx17 in the hippocampus markedly rescued the Meth-induced cognitive impairment and synaptic loss. For endosomes, Meth exposure upregulated Rab5 expression and its guanine-nucleotide exchange factor (GEF) (immature endosome), with a commensurate decreased active form of Rab7 (Rab7-GTP) and impeded the binding of Rab7 to CCZ1 (mature endosome); for autophagosomes, Meth treatment elicited a dramatic reduction in the overlap between Stx17 and autophagosomes but increased the colocalization of ATG5 and autophagosomes (immature autophagosomes). After Stx17 overexpression, the Rab7-GTP levels in purified late endosomes were substantially increased in parallel with the elevated mature autophagosomes, facilitating cargo (Aß42, p-tau, and EGFR) degradation in the vesicles, which finally ameliorated Meth-induced synaptic loss and memory deficits in mice. CONCLUSION: Stx17 decrease mediated by Meth contributes to vesicle fusion defects which may ascribe to the immature autophagosomes and endosomes, leading to autophagic dysfunction and finalizes neuronal damage and cognitive impairments. Therefore, targeting Stx17 may be a novel therapeutic strategy for Meth-induced neuronal injury.
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Autofagosomas , Autofagia , Animales , Ratones , Autofagosomas/metabolismo , Endosomas/metabolismo , Receptores ErbB/metabolismo , Factores de Intercambio de Guanina Nucleótido/metabolismo , Guanosina Trifosfato/metabolismoRESUMEN
AIMS: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an important technique for the treatment of refractory cardiogenic shock and cardiac arrest; however, the early management of ventricular fibrillation/ventricular tachycardia (VF/VT), within 72 h of VA-ECMO, and its effects on patient prognosis remain unclear. METHODS AND RESULTS: We retrospectively analysed patients at the First Affiliated Hospital of Nanjing Medical University who underwent VA-ECMO between January 2017 and March 2022. The patients were divided into two groups, VF/VT and nVF/VT, based on whether or not VF/VT occurred within 72 h after the initiation of VA-ECMO. We utilized logistic regression analysis to evaluate the independent risk factors for VF/VT in patients undergoing VA-ECMO and to ascertain whether the onset of VF/VT affected 28 day survival rate, length of intensive care unit stay, and/or other clinical prognostic factors. Subgroup analysis was performed for the VF/VT group to determine whether defibrillation affected prognosis. In the present study, 126 patients were included, 65.87% of whom were males (83/126), with a mean age of 46.89 ± 16.23, a 28 day survival rate of 57.14% (72/126), an incidence rate of VF/VT within 72 h of VA-ECMO initiation of 27.78% (35/126), and 80% of whom (28/35) received extracorporeal cardiopulmonary resuscitation. The incidence of VF/VT resulting from cardiac arrest at an early stage was significantly higher than that of refractory cardiogenic shock (80% vs. 20%; P = 0.022). The restricted cubic spline model revealed a U-shaped relationship between VF/VT incidence and initial heart rate (iHR), and multivariate logistic regression analysis showed that an iHR > 120 b.p.m. [odds ratio (OR) 6.117; 95% confidence interval (CI) 1.672-22.376; P = 0.006] and hyperlactataemia (OR 1.125; 95% CI 1.016-1.246; P = 0.023) within 1 h of VA-ECMO initiation were independent risk factors for the occurrence of VF/VT. VF/VT was not found to be associated with the 28 day survival of patients undergoing VA-ECMO support, nor did it affect other secondary endpoints. Defibrillation did not alter the overall prognosis in patients with VF/VT during VA-ECMO. CONCLUSIONS: An iHR > 120 b.p.m. and hyperlactataemia were independent risk factors for the occurrence of VF/VT within 72 h of VA-ECMO initiation. The occurrence of VF/VT does not affect, nor does defibrillation in these patients improve the overall patient prognosis. TRIAL REGISTRATION: ChiCTR1900026105.
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Oxigenación por Membrana Extracorpórea , Paro Cardíaco , Taquicardia Ventricular , Masculino , Humanos , Adulto , Persona de Mediana Edad , Femenino , Fibrilación Ventricular/epidemiología , Fibrilación Ventricular/etiología , Fibrilación Ventricular/terapia , Oxigenación por Membrana Extracorpórea/métodos , Incidencia , Choque Cardiogénico/epidemiología , Choque Cardiogénico/etiología , Choque Cardiogénico/terapia , Estudios Retrospectivos , Taquicardia Ventricular/epidemiología , Taquicardia Ventricular/etiología , Taquicardia Ventricular/terapia , Paro Cardíaco/epidemiología , Paro Cardíaco/terapia , Paro Cardíaco/etiología , Factores de RiesgoRESUMEN
We used manganese (Mn)-tolerant 'Xuegan' (Citrus sinensis) seedlings as materials and examined the characterization of Mn uptake and Mn-activated-release of root exudates under hydroponic conditions. We observed that root and shoot Mn bioaccumulation factor (BCF) reduced with the increase of Mn supply, and that Mn transfer factor (Tf) reduced greatly as Mn supply increased from 0 to 500 µM, beyond which Tf slightly increased with increasing Mn supply, suggesting that Mn supply reduced the ability to absorb and accumulate Mn in roots and shoots, as well as root-to-shoot Mn translocation. Without Mn, roots alkalized the solution pH from 5.0 to above 6.2, while Mn supply reduced root-induced alkalization. As Mn supply increased from 0 to 2000 µM, the secretion of root total phenolics (TPs) increased, while the solution pH decreased. Mn supply did not alter the secretion of root total free amino acids, total soluble sugars, malate, and citrate. Mn-activated-release of TPs was inhibited by low temperature and anion channel inhibitors, but not by protein biosynthesis inhibitor. Using widely targeted metabolome, we detected 48 upregulated [35 upregulated phenolic compounds + 13 other secondary metabolites (SMs)] and three downregulated SMs, and 39 upregulated and eight downregulated primary metabolites (PMs). These findings suggested that reduced ability to absorb and accumulate Mn in roots and shoots and less root-to-shoot Mn translocation in Mn-toxic seedlings, rhizosphere alkalization, and Mn-activated-release of root exudates (especially phenolic compounds) contributed to the high Mn tolerance of C. sinensis seedlings.
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Citrus sinensis , Citrus , Manganeso/farmacología , Manganeso/metabolismo , Citrus/metabolismo , Rizosfera , Raíces de Plantas/metabolismo , Plantones/metabolismoRESUMEN
Kodamaea ohmeri (K. ohmeri) is an ascosporogenic species of yeast that belongs to the genus Ascosporogenous and the family of Saccharomycetaceae. It has recently been found to cause various types of infections, particularly in critically ill immunocompromised patients. The present study describes a case of hospital-acquired pneumonia caused by K. ohmeri during veno-arterial extracorporeal membrane oxygenation. The fungal culture turned negative after the administration of caspofungin and amphotericin B. Extracorporeal membrane oxygenation (ECMO) is an adjunctive medical technique that provides temporary cardiopulmonary support for patients. Previous observations have suggested that the immune function of patients will typically decline during the use of ECMO, rendering infection to be one of the main complications of ECMO. K. ohmeri is a rare pathogenic fungus, particularly in immunocompromised individuals with vascular catheters, while amphotericin B is the most common antifungal therapy administered to treat K. ohmeri infections. It is important to raise awareness of rare fungal infections and actively treat them.
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AIMS: To analyse spatial and temporal changes in the global burden of diabetes mellitus (DM) attributable to dietary factors from 1990 to 2019. MATERIALS AND METHODS: The burden of DM was analysed in terms of age-standardized disability-adjusted life-year (DALY) rates and age-standardized death rates (ASDRs), which were obtained from the Global Burden of Disease Study 2019, and their corresponding estimated annual percentage changes (EAPCs). RESULTS: The ASDR exhibited a decreasing trend (EAPC = -0.02), while the age-standardized DALY rate exhibited an increasing trend (EAPC = 0.65). Forty-four percent of the burden of DM was attributable to dietary factors, with the three largest contributors being high intake of red meat, high intake of processed meat, and low intake of fruit. Residence in a region with a high sociodemographic index (SDI) was associated with a diet low in whole grains and high in red meat and processed meat, while residence in a low-SDI region was associated with a diet low in whole grains and fruits, and high in red meat. CONCLUSIONS: The age-standardized DALYs of DM attributable to dietary factors increased between 1990 and 2019 but differed among areas. The three largest dietary contributors to the burden of DM were high intake of red meat, high intake of processed meat, and low intake of fruit.
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Diabetes Mellitus , Carga Global de Enfermedades , Humanos , Diabetes Mellitus/epidemiología , Carne/efectos adversos , Frutas , Años de Vida Ajustados por Calidad de VidaRESUMEN
BACKGROUND: The ion shift index (ISI) as a prognostic indicator that can show the severity of hypoxic-ischemic injury. We aimed to evaluate the performance of the ISI in predicting unfavorable neurological outcomes at hospital discharge in cardiac arrest (CA) patients following extracorporeal cardiopulmonary resuscitation (ECPR) and to compare its performance to other prognostic predictors. METHODS: This was a retrospective observational study including adult CA patients treated with ECPR between January 2018 and December 2022 in a tertiary hospital. Data regarding clinical characteristics and laboratory parameters were collected from medical records. The ISI was determined based on the first available serum electrolyte levels after ECPR. The primary outcome was unfavorable neurological status at hospital discharge, defined as Cerebral Performance Categories 3-5. Comparisons of the characteristics between the two groups were made using the χ2 test for categorical variables and the t-test or non-parametric Mann-Whitney U-test for continuous variables, as appropriate. Correlation analysis was performed using Spearman's rank correlation coefficient. A two-tailed P-value <0.05 was considered statistically significant. RESULTS: Among the 122 patients involved, 46 (37.7%) had out-of-hospital CA, and 88 had unfavorable neurological outcomes. The ISI was significantly higher in the unfavorable outcome group than in the favorable outcome group (3.74 [3.15-4.57] vs. 2.69 [2.51-3.07], P<0.001). A higher ISI level was independently related to unfavorable outcome (odds ratio=6.529, 95% confidence interval 2.239-19.044, P=0.001). An ISI level >3.12 predicted unfavorable outcomes with a sensitivity and specificity of 74.6% and 85.2%, respectively (P<0.001). The prognostic performance of ISI (area under the curve [AUC]=0.887) was similar to that of other predictors, such as gray-to-white matter ratio (AUC=0.850, P=0.433) and neuron-specific enolase (AUC=0.925, P=0.394). CONCLUSION: ISI may be used as a prognostic biomarker to predict neurological outcomes in CA patients following ECPR.
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BACKGROUND: Severe trauma can result in cardiorespiratory failure, and when conventional treatment is ineffective, extracorporeal membrane oxygenation (ECMO) can serve as an adjunctive therapy. However, the indications for ECMO in trauma cases are uncertain and clinical outcomes are variable. This study sought to describe the prognosis of adult trauma patients requiring ECMO, aiming to inform clinical decision-making and future research. METHODS: A comprehensive search was conducted on Pubmed, Embase, Cochrane, and Scopus databases until March 13, 2023, encompassing relevant studies involving over 5 trauma patients (aged ≥ 16 years) requiring ECMO support. The primary outcome measure was survival until discharge, with secondary measures including length of stay in the ICU and hospital, ECMO duration, and complications during ECMO. Random-effects meta-analyses were conducted to analyze these outcomes. The study quality was assessed using the Joanna Briggs Institute checklist, while the certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS: The meta-analysis comprised 36 observational studies encompassing 1822 patients. The pooled survival rate was 65.9% (95% CI 61.3-70.5%). Specifically, studies focusing on traumatic brain injury (TBI) (16 studies, 383 patients) reported a survival rate of 66.1% (95% CI 55.4-76.2%), while studies non-TBI (15 studies, 262 patients) reported a survival rate of 68.1% (95% CI 56.9-78.5%). No significant difference was observed between these two survival comparisons (p = 0.623). Notably, studies utilizing venoarterial extracorporeal membrane oxygenation (VA ECMO) (15 studies, 39.0%, 95% CI 23.3-55.6%) demonstrated significantly lower survival rates than those using venovenous extracorporeal membrane oxygenation (VV ECMO) (23 studies, 72.3%, 95% CI 63.2-80.7%, p < 0.001). The graded assessment of evidence provided a high degree of certainty regarding the pooled survival. CONCLUSIONS: ECMO is now considered beneficial for severely traumatized patients, improving prognosis and serving as a valuable tool in managing trauma-related severe cardiorespiratory failure, haemorrhagic shock, and cardiac arrest.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Oxigenación por Membrana Extracorpórea , Insuficiencia Respiratoria , Humanos , Adulto , Pronóstico , Insuficiencia Respiratoria/terapia , Tasa de Supervivencia , Estudios RetrospectivosRESUMEN
BACKGROUND: We used a genome-wide discovery approach to identify methylation markers associated with metastasis in men with localized prostate cancer (PCa), as better identification of those at high risk of metastasis can inform treatment decision-making. METHODS: We identified men with localized PCa at Kaiser Permanente California (January 1, 1997-December 31, 2006) who did not receive curative treatment and followed them for 10 years to determine metastasis status. Cases were chart review-confirmed metastasis, and controls were matched using density sampling. We extracted DNA from the cancerous areas in the archived diagnostic tissue blocks. We used Illumina's Infinium MethylationEPIC BeadChip for methylation interrogation. We used conditional logistic regression and Bonferroni's correction to identify methylation markers associated with metastasis. In a separate validation cohort (2007), we evaluated the added predictive utility of the methylation score beyond clinical risk score. RESULTS: Among 215 cases and 404 controls, 31 CpG sites were significantly associated with metastasis status. Adding the methylation score to the clinical risk score did not meaningfully improve the c-statistic (0.80-0.81) in the validation cohort, though the score itself was statistically significant (p < 0.01). In the validation cohort, both clinical risk score alone and methylation marker score alone are well calibrated for predicted 10-year metastasis risks. Adding the methylation score to the clinical risk score only marginally improved predictive risk calibration. CONCLUSION: Our findings do not support the use of these markers to improve clinical risk prediction. The methylation markers identified may inform novel hypothesis in the roles of these genetic regions in metastasis development.