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BACKGROUND: Elderly hemodialysis (HD) patients have a high risk of death. The effect of different types of HD membranes on survival is still controversial. The purpose of this study was to determine the relationship between the use of low-flux or high-flux membranes and all-cause and cardiovascular mortality in elderly hemodialysis patients. METHODS: This was a retrospective clinical study involving maintenance hemodialysis patients which were categorized into low-flux and high-flux groups according to the dialyzer they were using. Propensity score matching was used to balance the baseline data of the two groups. Survival rates were compared between the two groups, and the risk factors for death were analyzed by multivariate Cox regression. RESULTS: Kaplan-Meier survival analysis revealed no significant difference in all-cause mortality between the low-flux group and the high-flux group (log-rank test, p = 0.559). Cardiovascular mortality was significantly greater in the low-flux group than in the high-flux group (log-rank test, p = 0.049). After adjustment through three different multivariate models, we detected no significant difference in all-cause mortality. Patients in the high-flux group had a lower risk of cardiovascular death than did those in the low-flux group (HR = 0.79, 95% CI, 0.54-1.16, p = 0.222; HR = 0.58, 95% CI, 0.37-0.91, p = 0.019). CONCLUSIONS: High-flux hemodialysis was associated with a lower relative risk of cardiovascular mortality in elderly MHD patients. High-flux hemodialysis did not improve all-cause mortality rate. Differences in urea distribution volume, blood flow, and systemic differences in solute clearance by dialyzers were not further analyzed, which are the limitations of this study.
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Doenças Cardiovasculares , Falência Renal Crônica , Humanos , Idoso , Falência Renal Crônica/complicações , Estudos Retrospectivos , Membranas Artificiais , Diálise Renal/efeitos adversosRESUMO
OBJECTIVE: Sotos syndrome (SOTOS) is an uncommon genetic condition that manifests itself with the following distinctive features: prenatal overgrowth, facial abnormalities, and intellectual disability. This disorder is often associated with haploinsufficiency of the nuclear receptor-binding SET domain protein 1 (NSD1)gene. We investigated four pediatric cases characterized by early-onset overgrowth and developmental delay. The primary objective of this study was to achieve accurate genetic diagnoses. DESIGN&METHODS: A sequential analysis approach comprising chromosomal karyotyping, whole exome sequencing, and microarray analysis was conducted. RESULTS: All four cases exhibited variations in the NSD1 gene, with the identification of four previously unreported de novo variants, each specific to one case.Specifically, Case 1 carried the NSD1 (NM_022455): c.2686 C > T(p.Q896X) variant, Case 2 had the NSD1 (NM_022455): c.2858_2859delCT(p.S953X) variant, Case 3 displayed a chromosomal aberration, chr5: 5q35.2q35.3(176,516,604-176,639,249)×1, which encompassed the 5'-untranslated region of NSD1, and Case 4 harbored the NSD1 (NM_022455): c.6397T > G(p.C2133G) variant. CONCLUSION: This study not only provided precise diagnoses for these cases but also supplied significant evidence to facilitate informed consultations. Furthermore, our findings expanded the spectrum of mutations associated with SOTOS.
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Histona-Lisina N-Metiltransferase , Síndrome de Sotos , Humanos , Histona-Lisina N-Metiltransferase/genética , Síndrome de Sotos/genética , Masculino , Feminino , Pré-Escolar , Criança , Lactente , Peptídeos e Proteínas de Sinalização Intracelular/genética , Sequenciamento do Exoma , Mutação , Cariotipagem , Histona Metiltransferases/genética , Proteínas Nucleares/genéticaRESUMO
OBJECTIVE: To investigate the relationship between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and all-cause and cardiovascular (CV) mortality in Chinese haemodialysis (HD) patients. DESIGN: Retrospective cohort study. SETTING: Patients from June 2015 to September 2016 and followed through September 2021 were categorised into quartiles according to the follow-up averaged TG/HDL-C ratio. The association between TG/HDL-C and mortality was examined by univariate and multivariate time-varying Cox regression analyses. The C-index was used to assess the predictive accuracy of the Cox regression models. PARTICIPANTS: A total of 534 maintenance HD patients were enrolled. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcomes were all-cause death and CV mortality. RESULTS: During the median follow-up of 61 months, 207 patients died, with 94 (45.4%) classified as CV death. After adjusting for confounders, multivariate time-varying Cox regression analysis showed that the quartile 4 group (TG/HDL-C ≥2.64) was associated with decreased all-cause mortality (adjusted HR 0.51, 95% CI 0.33-0.77, p=0.001) and CV mortality (adjusted HR 0.31; 95% CI 0.16 to 0.62; p=0.001) in maintenance HD patients. Model 1 of all-cause mortality achieved a C-index of 0.72 (95% CI 0.68 to 0.75), and model 2 achieved a C-index of 0.77 (95% CI 0.73 to 0.82). The C-index for model 1 in CV mortality was 0.74 (95% CI 0.70 to 0.77), and the C-index for model 2 was 0.80 (95% CI 0.75 to 0.84). CONCLUSIONS: High TG/HDL-C was associated with decreased all-cause and CV mortality in HD patients.
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Doenças Cardiovasculares , Humanos , HDL-Colesterol , Triglicerídeos , Estudos Retrospectivos , Diálise Renal , China/epidemiologia , Fatores de RiscoRESUMO
Gestational diabetes mellitus (GDM) with intrauterine hyperglycemia induces a series of changes in the placenta, which have adverse effects on both the mother and the fetus. The aim of this study was to investigate the changes in the placenta in GDM and its gender differences. In this study, we established an intrauterine hyperglycemia model using ICR mice. We collected placental specimens from mice before birth for histological observation, along with tandem mass tag (TMT)-labeled proteomic analysis, which was stratified by sex. When the analysis was not segregated by sex, the GDM group showed 208 upregulated and 225 downregulated proteins in the placenta, primarily within the extracellular matrix and mitochondria. Altered biological processes included cholesterol metabolism and oxidative stress responses. After stratification by sex, the male subgroup showed a heightened tendency for immune-related pathway alterations, whereas the female subgroup manifested changes in branched-chain amino acid metabolism. Our study suggests that the observed sex differences in placental protein expression may explain the differential impact of GDM on offspring.
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Diabetes Gestacional , Hiperglicemia , Humanos , Gravidez , Feminino , Masculino , Camundongos , Animais , Placenta/metabolismo , Proteômica , Camundongos Endogâmicos ICR , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismo , Hiperglicemia/genéticaRESUMO
BACKGROUND: Cardiovascular death is the main cause of death in patients with end-stage kidney disease (ESKD). Left ventricular hypertrophy (LVH) and left atrial diameter (LAD) enlargement are frequent cardiac alterations in patients with ESKD and are major risk factors for cardiovascular events. However, it remains unclear whether there is an association between combined LAD or LVH and all-cause or cardiovascular mortality in this population. METHODS: A single-centre, retrospective cohort study including 576 haemodialysis (HD) patients was conducted. Patients were evaluated by cardiac ultrasound, and the study cohort was divided into four groups according to LAD and LVH status: low LAD and non-LVH; low LAD and LVH; high LAD and non-LVH; and high LAD and LVH. We used Kaplan-Meier analysis and Cox proportional hazard regression to analyse all-cause and cardiovascular mortality after multivariate adjustment. RESULTS: LAD was associated with an increased risk of all-cause mortality (HR 2.371, 1.602-3.509; p < 0.001). No significant differences were found between LVH and the risk of all-cause mortality. Patients with high LAD and LVH had significantly greater all-cause and cardiovascular mortality than did those with low LAD and non-LVH after adjustments for numerous potential confounders (HR 3.080, 1.608-5.899; p = 0.001) (HR 4.059, 1.753-9.397; p = 0.001). CONCLUSION: Among maintenance haemodialysis (MHD) patients, LAD was more strongly associated with mortality than was LVH. A high LAD and LVH are associated with a greater risk of mortality. Our results emphasize that the occurrence of LAD and LVH in combination provides information that may be helpful in stratifying the risk of MHD patients.
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Átrios do Coração , Hipertrofia Ventricular Esquerda , Falência Renal Crônica , Diálise Renal , Humanos , Estudos Retrospectivos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/mortalidade , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Falência Renal Crônica/terapia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/complicações , Estimativa de Kaplan-Meier , Fatores de Risco , Modelos de Riscos Proporcionais , Causas de Morte , Medição de Risco , EcocardiografiaRESUMO
BACKGROUND: Depression is a prevalent mood disorder during the perioperative period, with both preoperative concurrent depression and new-onset postoperative depression impacting postoperative recovery. Recent studies have indicated that the dissociative anesthetic esketamine may alleviate perioperative depressive symptoms. OBJECTIVE: This meta-analysis aimed to assess the efficacy and safety of esketamine in treating perioperative depression. METHODS: We selected randomized controlled trials comparing esketamine to placebo in terms of postoperative depressive symptoms. The primary outcome was postoperative depression scores, with secondary outcomes including the prevalence of postoperative depression, pain scores using the Visual Analogue Scale or Numeric Rating Scale, and incidences of adverse reactions such as nausea/vomiting, dizziness, dreams/nightmares, hallucinations. RESULTS: We enrolled a total of 17 studies involving 2462 patients. The esketamine group demonstrated a significant reduction in postoperative depression scores within one week after surgery (SMD -0.47, 95% CI (-0.66, -0.27), P < 0.001) and over the long term (SMD -0.44, 95% CI (-0.79, -0.09), P = 0.01). Furthermore, esketamine significantly decreased the prevalence of postoperative depression both within one week (RR 0.46, 95% CI (0.33, 0.63), P < 0.001) and over the long term (RR 0.50, 95% CI (0.36, 0.70), P < 0.001). Additionally, esketamine effectively relieved pain on the first postoperative day compared to control. However, it also increased the risks of dizziness and hallucinations for a short time. CONCLUSION: This meta-analysis suggests that the intraoperative or postoperative application of esketamine could be a potentially effective treatment for perioperative depression, although the increased risk of adverse reactions should be considered.
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Procedimentos Cirúrgicos Eletivos , Ketamina , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Depressão/tratamento farmacológico , Período PerioperatórioRESUMO
Respiration is essential for supporting human body functions. However, a biocompatible fiber respiration sensor has rarely been discussed. In this study, we propose a wearable fiber surface plasmon resonance (SPR) respiration sensor using a LiBr-doped silk fibroin (SF) film. The SPR sensor monitors respiration by responding to airway humidity variation during inhalation and exhalation. We fabricated the SPR respiration sensor by depositing the core of a plastic-clad optical fiber with a gold film and an SF-LiBr composite film. The SF-LiBr composite film can absorb water through the interaction between water molecules and hydrogen bonds linking fibroin chains. Thus, humidity variation can change the SF-LiBr composite film's refractive index (RI), altering the phase-matching condition of the surface plasmon polaritons and shifting the SPR spectral dip. In experiments, we test the effect of the LiBr doping ratio on humidity response and confirm that the SF-22.1 wt % LiBr sensor has balanced performances. The SF-22.1 wt % LiBr sensor has a broad sensing range of 35-99% relative humidity (RH), a reasonable overall sensitivity of -6.5 nm/% RH, a fast response time of 135 ms, a quick recovery time of 150 ms, good reversibility, and good repeatability, which is capable of tracking different respiration states and patterns. Finally, we encapsulate this sensor in a conventional nasal oxygen cannula for wearable respiration monitoring, proving that the sensor is suitable for high-sensitivity, real-time, and accurate respiration monitoring.
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Fibroínas , Dispositivos Eletrônicos Vestíveis , Humanos , Ressonância de Plasmônio de Superfície , Respiração , ÁguaRESUMO
Alzheimer's disease (AD) is a primary neurodegenerative disease. It can be caused by aging and brain trauma and severely affects the abilities of cognition and memory of patients. Therefore, it seriously threatens the mental and physical health of humans worldwide. As a traditional Chinese medicine, ginsenosides have been proven to have a variety of pharmacological activities. Ginsenoside Rh4 (Rh4) is one of the rare ginsenosides with higher pharmacological activity than ordinary ginsenosides, but its effect on alleviating AD and its molecular mechanism have not been studied. Here, we investigated the anti-AD effects of Rh4 and its potential mechanisms using an AD mouse model induced by a combination of AlCl3·6H2O and d-galactose. The results showed that Rh4 could significantly improve the ability of cognizance and reduce neuronal damage in mice. Concurrently, Rh4 attenuates amyloid ß accumulation, increases the density of dendritic spines, and logically inhibits synaptic structural damage as a result of neuronal excessive apoptosis and autophagy. Rh4 can not only inhibit the inflammatory response caused by the overactivation of microglia and astrocytes, reduce the levels of pro-inflammatory factors, increase the level of antioxidant enzymes in serum, and significantly improve the activity of antioxidant enzyme SOD1 in the hippocampus but also inhibit the hyperphosphorylation of tau protein in the hippocampus of mice by regulating the Wnt2b/GSK-3ß/SMAD4 signaling pathway. Together, this study provides a theoretical basis for Rh4 in the treatment of AD and reveals that Rh4 is a potential drug for the treatment of AD.
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Doença de Alzheimer , Ginsenosídeos , Doenças Neurodegenerativas , Humanos , Animais , Camundongos , Peptídeos beta-Amiloides/genética , Proteínas tau/genética , Ginsenosídeos/farmacologia , Glicogênio Sintase Quinase 3 beta/genética , Doenças Neuroinflamatórias , Antioxidantes , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Transdução de SinaisRESUMO
PURPOSE: The aim of this study was to further assess whether the platelet-to-lymphocyte ratio (PLR) is independently associated with all-cause mortality and cardiovascular mortality in maintenance hemodialysis (MHD) patients. METHODS: From January 1, 2014, to December 31, 2014, patients undergoing regular hemodialysis in the Blood Purification Center of the General Hospital of Northern Theatre Command were retrospectively selected. A total of 303 MHD patients were enrolled in accordance with the inclusion and exclusion criteria. For each patient, the endpoint of follow-up was either death or December 31, 2021. The primary endpoints were all-cause and cardiovascular death. A receiver operating characteristic (ROC) curve was drawn to detect the predictive ability of PLR, and the optimal critical value of PLR was determined to be 107.57. Kaplan-Meier curves and Cox proportional analysis were used to assess the prognostic value of PLR. We used the same method to evaluate the correlation between the neutrophil-to-lymphocyte ratio (NLR) and the prognosis of MHD patients. RESULTS: At the end of follow-up, 128 MHD patients had progressed to all-cause death, and 73 MHD patients had progressed to cardiovascular death. In multivariate Cox regression, both the high PLR group and the high NLR group were independently associated with all-cause mortality (HR 2.608, 95% CI 1.579-4.306, p < .001 vs. HR 1.634, 95% CI 1.023-2.610, p = .04). Only high PLR expression was associated with cardiovascular mortality (HR 3.379, 95% CI 1.646-6.936, p = .001). CONCLUSIONS: High PLR levels can independently predict all-cause and cardiovascular mortality in MHD patients.
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Doenças Cardiovasculares , Sistema Cardiovascular , Humanos , Estudos Retrospectivos , Linfócitos , Diálise RenalRESUMO
BACKGROUND: Postpartum depression (PPD) is a prevalent public health issue. Although ketamine has prophylactic effects on PPD in women undergoing cesarean section, the effects of esketamine on PPD remain unclear. This trial aimed to evaluate the efficacy of perioperative esketamine infusion on PPD risk by assessing Edinburgh Postnatal Depression Scale (EPDS) scores and blood biomarkers. METHODS: A total of 150 participants undergoing elective cesarean section were randomly allocated to receive either esketamine or normal saline. Since 27 participants were excluded due to consent withdrawal or loss to follow-up, 123 patients were included. The primary outcome was the prevalence of PPD risk. Secondary outcomes included the prevalence of postpartum anxiety (PPA) risk, levels of biomarkers, postoperative pain intensity, and cumulative sufentanil consumption. RESULTS: The prevalence of PPD and PPA risk at 3 days, 42 days, 3 months, and 6 months postpartum did not differ between the two groups. Furthermore, EPDS scores, pain intensity at rest, and during coughing on postoperative days (POD) 1 and 2 did not differ between the two groups. Sufentanil consumption during 0-12 h, 12-24 h, 0-24 h, and 0-48 h postoperatively were significantly lower in the esketamine group compared to the control group. Blood biomarkers did not differ between the two groups on POD 3. LIMITATIONS: The sample size was small. PPD risk was simply screened, not diagnosed. CONCLUSIONS: Perioperative administration of esketamine did not decrease the incidence of PPD risk in women after elective cesarean section. However, esketamine reduced opioid consumption.
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Depressão Pós-Parto , Ketamina , Humanos , Feminino , Gravidez , Cesárea/efeitos adversos , Ketamina/uso terapêutico , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/prevenção & controle , Sufentanil/uso terapêutico , BiomarcadoresRESUMO
The Fiber SPR chip laboratory has become a popular choice in biochemical detection. To meet the needs of different kinds of analytes for the detection range and number of channels of the chip, we proposed a multi-mode SPR chip laboratory based on microstructure fiber in this paper. The chip laboratory was integrated with microfluidic devices made from PDMS and detection units made of bias three-core fiber and dumbbell fiber. By injecting light into different cores of a bias three-core fiber, different detection areas of dumbbell fiber can be selected, enabling the chip laboratory to enter high refractive index detection, multi-channel detection and other working modes. In the high refractive index detection mode, the chip can detect liquid samples with a refractive index range of 1.571-1.595. In multi-channel detection mode, the chip can achieve dual parameter detection of glucose and GHK-Cu, with sensitivities of 4.16â nm/(mg/mL) and 9.729â nm/(mg/mL), respectively. Additionally, the chip can switch to temperature compensation mode. The proposed multi working mode SPR chip laboratory, based on micro structured fiber, offers a new approach for the development of portable testing equipment that can detect multiple analytes and meet multiple requirements.
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BACKGROUND: Helicobacter pylori (H. pylori) infection is a global problem, causing significant morbidity and mortality. Furazolidone is recommended to eradicate H. pylori infections in China owing to the highly associated antibiotic resistance. CASE SUMMARY: This article presents two cases of lung injury caused by furazolidone treatment of H. pylori infection and the relevant literature review. Two patients developed symptoms, including fever, cough, and fatigue after receiving a course of furazolidone for H. pylori infection. Chest computed tomography showed bilateral interstitial infiltrates. Laboratory studies revealed elevated blood eosinophil count. After discontinuing furazolidone with or without the use of corticosteroids, the symptoms improved rapidly. A PubMed database literature search revealed three reported cases of lung injury suggestive of furazolidone-induced pulmonary toxicity. CONCLUSION: Clinicians should be aware of the side effects associated with the administration of furazolidone to eradicate H. pylori infection.
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The concentration of tumor markers is low, which needs a highly sensitive, stable and fast detection method. In this paper, we proposed and demonstrated a U-shape fiber SPR biosensor sensitized by MOFs materials. The surface of the U-shape SPR sensor was modified with MOFs materials to enhance the sensitivity, and the nucleic acid aptamer was immobilized on the sensor surface because of the biocompatibility of MOFs materials. By the high specificity of the nucleic acid aptamer, the MUC1 protein was recognized and detected. The testing results indicate that the sensor has a logarithmic linear response in the MUC1 protein concentration detection range of 1 pg/ml-100 µg/ml, its sensitivity and detection limit are 5.33 nm/log(µg/ml) and 0.16 pg/ml respectively. After being sensitized by MOFs, the detection sensitivity of the sensor can be increased by 1.62 timesï¼the LOD can be decreased by 0.75 times. The sensor has high sensitivity and specificity, which has broad application prospects in clinical detection of tumor markers.
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Técnicas Biossensoriais , Ácidos Nucleicos , Ressonância de Plasmônio de Superfície , Técnicas Biossensoriais/métodos , Biomarcadores TumoraisRESUMO
Background: Congenital heart disease (CHD) is the most common birth defect with strong genetic heterogeneity. To date, about 400 genes have been linked to CHD, including cell signaling molecules, transcription factors, and structural proteins that are important for heart development. Genetic analysis of CHD cases is crucial for clinical management and etiological analysis. Methods: Whole-exome sequencing (WES) was performed to identify the genetic variants in two independent CHD cases with DNA samples from fetuses and their parents, followed by the exclusion of aneuploidy and large copy number variations (CNVs). The WES results were verified by Sanger sequencing. Results: In family A, a compound heterozygous variation in PLD1 gene consisting of c.1132dupA (p.I378fs) and c.1171C>T (p.R391C) was identified in the fetus. The two variants were inherited from the father (c.1132dupA) and the mother (c.1171C>T), respectively. In family B, a hemizygous variant ZIC3: c.861delG (p.G289Afs*119) was identified in the fetus, which was inherited from the heterozygous mother. We further confirmed that these variants PLD1: c.1132dupA and ZIC3: c.861delG were novel. Conclusion: The findings in our study identified novel variants to the mutation spectrum of CHD and provided reliable evidence for the recurrent risk and reproductive care options to the affected families. Our study also demonstrates that WES has considerable prospects of clinical application in prenatal diagnosis.
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Purpose: Abdominal aortic calcification (AAC) assessed by using standard lateral lumbar radiographs can be graded, and composite summary scores (range, 0-24) have been shown to be highly predictive of subsequent cardiovascular morbidity and mortality in hemodialysis (HD) patients. However, few studies have sought to determine the optimal AAC score cutoff values for the prediction of mortality among HD patients.Methods: This retrospective cohort study included 408 hemodialysis patients. AAC severity was quantified by the AAC score, which was measured by lateral lumbar radiography with complete follow-up data from January 2015 to December 2021. We used receiver operating characteristic (ROC) analysis to find the cutoff AAC value for the prediction of mortality. The Kaplan-Meier method was used to analyze all-cause and cardiovascular mortality.Results: The cutoff calcification score for the prediction of mortality was 4.5 (sensitivity, 67.3%; specificity, 70.4%). The patients with AAC scores above 4.5 had significantly higher all-cause (log-rank p < 0.001) and cardiovascular (log-rank p < 0.001) mortality rates than those with AAC scores below 4.5. In the multivariate regression analyses, an AAC score above 4.5 was a significant factor associated with all-cause mortality (HR: 2.079, p = 0.002) and cardiovascular mortality (HR: 2.610, p < 0.001).Conclusions: AAC is a reliable aortic calcification marker. HD patients with an AAC score > 4.5 have significantly elevated all-cause and cardiovascular mortality compared with those with an AAC score ≤ 4.5. AAC was a better predictor than cardiac valve calcification for mortality in HD patients.
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Doenças da Aorta , Calcificação Vascular , Humanos , Estudos Retrospectivos , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/etiologia , Fatores de Risco , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/complicações , Diálise Renal/efeitos adversosRESUMO
Ketamine can produce rapid-acting antidepressant effects in treatment-resistant patients with depression. Although alterations in glutamatergic and GABAergic neurotransmission in the brain play a role in depression, the precise molecular mechanisms in these neurotransmission underlying ketamine's antidepressant actions remain largely unknown. Mice exposed to FSS (forced swimming stress) showed depression-like behavior and decreased levels of GABA (γ-aminobutyric acid), but not glutamate, in the hippocampus. Ketamine increased GABA levels and decreased glutamate levels in the hippocampus of mice exposed to FSS. There was a correlation between GABA levels and depression-like behavior. Furthermore, ketamine increased the levels of enzymes and transporters on the GABAergic neurons (SAT1, GAD67, GAD65, VGAT and GAT1) and astrocytes (EAAT2 and GAT3), without affecting the levels of enzymes and transporters (SAT2, VGluT1 and GABAAR γ2) on glutamatergic neurons. Moreover, ketamine caused a decreased expression of GABAAR α1 subunit, which was specifically expressed on GABAergic neurons and astrocytes, an increased GABA synthesis and metabolism in GABAergic neurons, a plasticity change in astrocytes, and an increase in ATP (adenosine triphosphate) contents. Finally, GABAAR antagonist bicuculline or ATP exerted a rapid antidepressant-like effect whereas pretreatment with GABAAR agonist muscimol blocked the antidepressant-like effects of ketamine. In addition, pharmacological activation and inhibition of GABAAR modulated the synthesis and metabolism of GABA, and the plasticity of astrocytes in the hippocampus. The present data suggest that ketamine could increase GABA synthesis and astrocyte plasticity through downregulation of GABAAR α1, increases in GABA, and conversion of GABA into ATP, resulting in a rapid-acting antidepressant-like action. This article is part of the Special Issue on 'Ketamine and its Metabolites'.
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Ketamina , Receptores de GABA-A , Camundongos , Animais , Receptores de GABA-A/metabolismo , Ketamina/uso terapêutico , Antidepressivos/farmacologia , Antidepressivos/metabolismo , Hipocampo/metabolismo , Antagonistas GABAérgicos , Neurônios GABAérgicos/metabolismo , Ácido gama-Aminobutírico/metabolismo , Depressão/tratamento farmacológicoRESUMO
There are few methods and insufficient accuracy for growth differentiation factor 11 (GDF11) concentration detection. In this paper, we designed a twisted fiber cladding surface plasmon resonance (SPR) sensor, which can achieve a high precision detection of GDF11 concentration. The new structure of the fiber cladding SPR sensor was realized by coupling the light in the fiber core to the cladding through fiber thermal fusion twisting micromachining technology; a series of functionalized modifications were made to the sensor surface to obtain a fiber sensor capable of GDF11 specific recognition. The experimental results showed when GDF11 antigen concentration was 1 pg/mL-10 ng/mL, the sensor had a detection sensitivity of 2.518 nm/lgC, a detection limit of 0.34 pg/mL, and a good log-linear relationship. The sensor is expected to play a role in the rapid and accurate concentration detection of pathological study for growth differentiation factors.
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Background: Cardiovascular disease (CVD) is a major cause of mortality in patients on haemodialysis. The development of a prediction model for CVD risk is necessary to help make clinical decisions for haemodialysis patients. This retrospective study aimed to develop a prediction model for the 5-year risk of CV events and all-cause mortality in haemodialysis patients in China. Methods: We retrospectively enrolled 398 haemodialysis patients who underwent dialysis at the dialysis facility of the General Hospital of Northern Theater Command in June 2016 and were followed up for 5 years. The composite outcome was defined as CV events and/or all-cause death. Multivariable logistic regression with backwards stepwise selection was used to develop our new prediction model. Results: Seven predictors were included in the final model: age, male sex, diabetes, history of CV events, no arteriovenous fistula at dialysis initiation, a monocyte/lymphocyte ratio greater than 0.43 and a serum uric acid level less than 436 mmol/L. Discrimination and calibration were satisfactory, with a C-statistic above 0.80. The predictors lay nearly on the 45-degree line for agreement with the outcome in the calibration plot. A simple clinical score was constructed to provide the probability of 5-year CV events or all-cause mortality. Bootstrapping validation showed that the new model also has similar discrimination and calibration. Compared with the Framingham risk score (FRS) and a similar model, our model showed better performance. Conclusion: This prognostic model can be used to predict the long-term risk of CV events and all-cause mortality in haemodialysis patients. An MLR greater than 0.43 is an important prognostic factor.
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Doenças Cardiovasculares , Diálise Renal , Humanos , Masculino , Estudos Retrospectivos , Diálise Renal/efeitos adversos , Ácido Úrico , Fatores de Risco , Doenças Cardiovasculares/epidemiologiaRESUMO
To further reduce the size of a microfluidic detection chip and the sample consumption and to shorten the chip manufacturing cycle, an all-fiber SPR detection multichannel microfluidic chip was proposed and demonstrated in this paper. The microfluidic channel of the proposed chip was provided by the air channel of a double side-hole fiber, the detection unit was fabricated using a dumbbell fiber with a fiber core exposed to air, and the sensing probe was composed and packaged by fiber micro-processing technology. The internal double channels of the fiber constructed from double side-hole and dumbbell fibers can realize dual channel detection based on space division multiplexing. 30 nm silver and 50 nm gold films were respectively coated on the left and right sides of the dumbbell fiber, which can realize the dual channel simultaneous detection based on wavelength division multiplexing. We employed the proposed microfluidic chip to detect immunoglobulin G and dopamine molecules, where the average sensitivity is 0.252 nm (mg mL-1)-1 and 0.061 nm (µg mL-1)-1, and the LOD is 0.397 mg mL-1 and 1.639 µg mL-1, respectively. The microfluidic channel and detection unit of all-fiber multi-channel SPR detection microfluidic chip are provided by a soft and flexible fiber, which is compact in structure, flexible in fabrication and short in manufacturing cycle, making it possible for the microfluidic chip to enter the human body for detection and enabling a new approach for the fabrication of wearable detection microfluidic devices. This provides a new idea for the development of microfluidic chips.
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Técnicas Analíticas Microfluídicas , Humanos , Microfluídica , Ouro/química , PrataRESUMO
BACKGROUND: HMO (Hereditary Multiple Osteochondroma), an uncommon autosomal dominant disorder, is characterized by the development of multiple osteochondromas, which are nonmalignant cartilage-capped bone tumors growing outwards from long bone metaphyses. METHODS: The present work retrospectively analyzed seven children with HMO who were enrolled for routine clinical diagnosis and treatment, including X-ray examination. Subsequent genetic detection was carried out using whole exome sequencing (WES). In addition, this work applied Sanger sequencing to be the validation approach. Moreover, this work also examined amino acid (AA) evolutionary conservatism under the influence of certain missense variants. RESULTS: The clinical indications of all seven patients and their family members were thoroughly indexed. WES identified diagnostic variants in the EXT1 or EXT2 gene in these patients. In these variants, four were reported for the first time, namely EXT1: c.1285-2A>T, EXT2: c.1139delT, EXT1: c.203G>A, and EXT1: c.1645_1673del. Familial validation revealed that three of the variants were hereditary, while the other four were de novo, which was consistent with the phenotype in each case. CONCLUSION: Our results expanded HMO variation spectrum, and laid certain foundations for the precise counseling of those affected families.