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OBJECTIVE: The aim of our study was to evaluate the indocyanine green (ICG) retention test as a noninvasive marker of esophageal varices(EV). METHODS: The clinical data of patients diagnosed with compensated liver cirrhosis in Tianjin Second People's Hospital between January 2018 and January 2021 were analysed with SPSS 23.0. RESULT: A total of 144 patients (88 M/56 F, 51.7 ± 11.06 years) were enrolled. The ICG retention at 15 min(ICG-r15), PVD, TBIL, Cholinesterase(CHE), AST to ALT ratio(ARR), APRI, splenic area, Lok index, Park index and liver stiffness measurement in the absent or small EV group were lower than those in the medium or large EV group, while the ICG disappareance rate(ICG-K), Effective hepatic blood flow(EHBF), ALB, PLT, and Platelet to Spleen Diameter Ratio(PSDR) were higher, and the differences were significant (P < 0.05). ICG-r15, splenic area, APRI and PLT were independent predictors for medium or large esophageal varices (OR = 1.115, 1.025, 0.281, and 0.987, respectively,P < 0.05). The predictive value of ICG-r15 for medium or large varices was 17.95%, the specificity was 0.849, and the sensitivity was 0.662, the AUROC was 0.815. The cut-off value of PLT for M/L EV was 113.5, and the specificity and sensitivity were 0.616 and 0.887, the AUROC was 0.759. The AUROC of ICG-r15 combined with PLT was 0.866, which was more superior than others. CONCLUSION: Although we are far from the replacement of endoscopy, ICG-r15 combined with PLT seems to be able to identify patients with medium or large EV in patients with compensated liver cirrhosis.
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Várices Esofágicas y Gástricas , Verde de Indocianina , Cirrosis Hepática , Valor Predictivo de las Pruebas , Humanos , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/diagnóstico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/sangre , Masculino , Femenino , Persona de Mediana Edad , Adulto , Biomarcadores/sangre , Bazo/patología , Bazo/diagnóstico por imagen , Colorantes , Recuento de Plaquetas , Curva ROC , Sensibilidad y EspecificidadRESUMEN
PURPOSE: Total-body dynamic positron emission tomography (PET) imaging with total-body coverage and ultrahigh sensitivity has played an important role in accurate tracer kinetic analyses in physiology, biochemistry, and pharmacology. However, dynamic PET scans typically entail prolonged durations ([Formula: see text]60 minutes), potentially causing patient discomfort and resulting in artifacts in the final images. Therefore, we propose a dynamic frame prediction method for total-body PET imaging via deep learning technology to reduce the required scanning time. METHODS: On the basis of total-body dynamic PET data acquired from 13 subjects who received [68Ga]Ga-FAPI-04 (68Ga-FAPI) and 24 subjects who received [68Ga]Ga-PSMA-11 (68Ga-PSMA), we propose a bidirectional dynamic frame prediction network that uses the initial and final 10 min of PET imaging data (frames 1-6 and frames 25-30, respectively) as inputs. The peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) were employed as evaluation metrics for an image quality assessment. Moreover, we calculated parametric images (68Ga-FAPI: [Formula: see text], 68Ga-PSMA: [Formula: see text]) based on the supplemented sequence data to observe the quantitative accuracy of our approach. Regions of interest (ROIs) and statistical analyses were utilized to evaluate the performance of the model. RESULTS: Both the visual and quantitative results illustrate the effectiveness of our approach. The generated dynamic PET images yielded PSNRs of 36.056 ± 0.709 dB for the 68Ga-PSMA group and 33.779 ± 0.760 dB for the 68Ga-FAPI group. Additionally, the SSIM reached 0.935 ± 0.006 for the 68Ga-FAPI group and 0.922 ± 0.009 for the 68Ga-PSMA group. By conducting a quantitative analysis on the parametric images, we obtained PSNRs of 36.155 ± 4.813 dB (68Ga-PSMA, [Formula: see text]) and 43.150 ± 4.102 dB (68Ga-FAPI, [Formula: see text]). The obtained SSIM values were 0.932 ± 0.041 (68Ga-PSMA) and 0.980 ± 0.011 (68Ga-FAPI). The ROI analysis conducted on our generated dynamic PET sequences also revealed that our method can accurately predict temporal voxel intensity changes, maintaining overall visual consistency with the ground truth. CONCLUSION: In this work, we propose a bidirectional dynamic frame prediction network for total-body 68Ga-PSMA and 68Ga-FAPI PET imaging with a reduced scan duration. Visual and quantitative analyses demonstrated that our approach performed well when it was used to predict one-hour dynamic PET images. https://github.com/OPMZZZ/BDF-NET .
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Objectives: CD8+ T cells play a critical role in the immune dysfunction associated with liver cirrhosis. CD38+HLA-DR+CD8+ T cells, or bystander-activated CD8+ T cells, are involved in tissue injury but their specific contribution to liver cirrhosis remains unclear. This study sought to identify the mechanism for CD38+HLA-DR+CD8+ T cell-mediated pathogenesis during liver cirrhosis. Methods: The immunophenotype, antigen specificity, cytokine secretion and cytotoxicity-related indicators of CD38+HLA-DR+CD8+ T cells were determined using flow cytometry. The functional properties of these cells were assessed using transcriptome analysis. CD38+HLA-DR+CD8+ T-cell killing was detected using cytotoxicity and antibody-blocking assays. Results: The proportion of CD38+HLA-DR+CD8+ T cells was significantly elevated in liver cirrhosis patients and correlated with tissue damage. Transcriptome analysis revealed that these cells had innate-like functional characteristics. This CD8+ T-cell population primarily consisted of effector memory T cells and produced a high level of cytotoxicity-related cytokines, granzyme B and perforin. IL-15 promoted CD38+HLA-DR+CD8+ T-cell activation and proliferation, inducing significant TCR-independent cytotoxicity mediated through NKG2D. Conclusions: CD38+HLA-DR+CD8+ T cells correlated with cirrhosis-related liver injury and contributed to liver damage by signalling through NKG2D in a TCR-independent manner.
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PURPOSE: The performance of detectors is key for a PET scanner to achieve high spatial resolution and high sensitivity. This work aims to develop flood histogram generating algorithms to reduce the edge effect and improve the crystal identification of a PET detector consisting of two optically coupled pixelated scintillator detectors. METHODS: The PET detector consists of two optically coupled detectors, each consisting of a 23×23 LYSO crystal array with a crystal size of 1.0×1.0×20 mm3 read out by an 8×8 SiPM array with a pixel size of 3.0×3.0 mm2. The SiPM array is read out with a resistor network circuit to obtain four position encoding energy signals. A novel center of gravity (COG) positioning algorithm using six signals from the two detectors was proposed and compared to the traditional COG algorithms using either four or eight signals from the detectors. The raised-to-the-power (RTP) method was applied to the three COG algorithms for the PET detector. Different powers of the RTP from 1.0 to 2.5 were evaluated. RESULTS: The proposed COG algorithm significantly improves the crystal identification at the junction of the two detectors as compared to the COG algorithm using four signals of each detector, and improves the crystal identification at the center of the two detectors as compared to the COG algorithm using eight signals from both detectors. The RTP method significantly improves the overall flood histogram qualities of the two COG algorithms using either eight or six signals from the two detectors, and the two COG algorithm provide similar flood histogram quality when a power of 1.5 is used. CONCLUSION: The novel positioning algorithms reduce the edge effect and improve the flood histogram quality for a PET detector consisting of two optically coupled detectors, each consisting of a pixelated scintillator crystal array and a SiPM array with highly multiplexed four signal readout. The positioning algorithms can be used in a PET scanner to improve the spatial resolution and sensitivity.
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BACKGROUND & AIMS: There are lots of risk factors reported for cirrhotic portal vein thrombosis (PVT) development, however, the relationship between hepatic venous pressure gradient (HVPG) and PVT development remains unclear. METHODS: The clinical outcomes of cirrhotic patients who had no PVT and underwent HVPG measurement at baseline between March 2018 and March 2022 were analyzed retrospectively. Screening for non-tumoral PVT development was implemented by contrast-enhanced computed tomography and/or magnetic resonance imaging every 6-12 months. RESULTS: Eighty-two cirrhotic patients were evaluated over a follow-up period. Of these, 12 patients (14.6%) experienced the development of PVT. The occurrence of non-tumoral PVT at one, two, and three years were 6.6%, 11.7%, and 22.2% respectively. HVPG (p=0.038;HR 1.07;95%CI 1.00-1.14) and alcohol liver disease (ALD) (p=0.019;HR 4.20;95%CI 1.27-13.89) were independently associated with a high PVT risk. The cutoff value of HVPG was 17.52 mmHg. The cumulative incidence of PVT differed significantly among groups stratified by HVPG thresholds of 16mmHg (P=0.011). The sensitivity and specificity of HVPG≥16mmHg in predicting PVT development were 100.0% and 35.7%. CONCLUSIONS: In patients with liver cirrhosis, the value of HVPG was the independent predictive factor of PVT development. Screening for PVT was recommended during follow-up in patients with HVPG≥16 mmHg.
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Nigrospora oryzae, a newly identified pathogen, is responsible for poplar leaf blight, causing significant harm to poplar growth. Here, we describe, for the first time, a biological control method for the control of poplar leaf blight via the applications of 3 dominant Trichoderma strains/species. In this study, dominant Trichoderma species/strains with the potential for biocontrol were identified and then further characterised via dual culture assays, volatile organic compounds (VOCs), and culture filtrates. The biocontrol efficacy of these strains against N. oryzae was found to exceed 60%. Furthermore, the reactive oxygen species (ROS) content in Populus davidiana × P. alba var. pyramidalis (PdPap) leaves pretreated with these Trichoderma strains significantly decreased. Furthermore, pretreatment of PdPap with a combination of these Trichoderma (Tcom) resulted in 9.71-fold and 1.95-fold increases in peroxidase (POD) and superoxide dismutase (SOD) activity, respectively, and 3.87-fold decrease in the MDA content compared to controls. Moreover, Tcom pretreatment activated the salicylic acid (SA) and jasmonic acid (JA) pathway-dependent defence responses of poplar, upregulating pathogenesis-related protein (PR) and MYC proto-oncogene (MYC-R) by more than 12-fold and 17.32-fold, respectively. In addition, Trichoderma treatments significantly increased the number of lateral roots, aboveground biomass, and stomata number and density of PdPap, and Tcom was superior to the single pretreatments. The soil pH also became weakly acidic in these pretreatments, which is beneficial for the growth of PdPap seedlings. These findings indicate that these dominant Trichoderma strains can effectively increase biocontrol and poplar growth promotion.
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Ascomicetos , Enfermedades de las Plantas , Hojas de la Planta , Populus , Populus/microbiología , Populus/metabolismo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Ascomicetos/fisiología , Hojas de la Planta/microbiología , Hojas de la Planta/metabolismo , Trichoderma/fisiología , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ácido Salicílico/metabolismo , Compuestos Orgánicos Volátiles/metabolismo , Agentes de Control BiológicoRESUMEN
The global spread of the Omicron variant strain BA.5/BF.7 has led to an increase in breakthrough infections. The elderly population shows different immune responses after infection due to the aging of the immune system, which has not been fully studied. The aim of this study was to investigate the effect of aging on immune response after breakthrough infection of Omicron BA.5/BF.7 variant, especially the changes of protein immune mechanism. The study analyzed the concentration of antibodies in serum and their ability to neutralize the mutant strain by comparing the immune response of the elderly population and the young population after infection. Proteomics techniques were used to assess differences in the expression of key proteins in immune cells of different age groups. The study found that older subjects produced lower levels of antibodies after infection than younger subjects and showed a significantly reduced ability to neutralize against BA.5/BF.7. In addition, proteomic analysis showed that the expression of proteins related to inflammation and apoptosis significantly increased in the immune cells of the elderly, while the proteins related to antiviral response and cell repair significantly decreased. These findings provide new ideas for immune intervention strategies in the elderly population, and emphasize the targeted research of anti-virus vaccines.
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OBJECTIVE: To compare the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) under facial feature point localization (FFP) localization versus neuro-navigated localization for depression. METHODS: 42 depressed patients were randomly assigned to two groups, received 10â¯Hz rTMS twice daily for 10 consecutive days. Relevant symptom scale assessments were conducted by professionals at baseline, after 10 sessions, and at the end of treatment. The confidence interval was calculated at a 95â¯% confidence level. The significant level was set at pâ¯<â¯0.05. RESULTS: The absolute change in HAMD total score from baseline to the end of therapy did not differ significantly between the groups. The generalized estimating equation showed the main effect of time was significant, which showed improvement of depressive symptoms in patients throughout treatment. Upon completion of the treatment, FFP group showed a response rate of 64.7â¯% and a remission rate of 29.4â¯%, whereas the navigated group exhibited a response rate of 61.1â¯% and a remission rate of 44.4â¯%. There was no serious adverse events occurred during the treatment process. Throughout the study, no intervention was made on the normal medication treatment, and some patients had concomitant antidepressants and benzodiazepines. CONCLUSION: There was no significant difference in clinical efficacy between FFP localization and navigation localization in the small-sample study. However, due to the limited sample size and lack of rigorous non-inferiority testing, the superiority of one over the other remains uncertain, necessitating rigorous experimental design to validate the efficacy difference between the two localization methods.
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OBJECTIVES: Neuregulin 1 (NRG1) is a risk gene for schizophrenia and involved in neurodevelopment and synaptic plasticity. Polymorphisms in NRG1 may affect psychotic symptoms in schizophrenia. This study investigated the effects of the single nucleotide polymorphism (SNP) rs6982890 on peripheral plasma NRG1 immunoreactivity, clinical symptoms and cognitive functions in schizophrenia patients. MATERIAL AND METHODS: We recruited subjects from the Han population of northern China from 2010 to 2022. We first genotyped and analyzed 6 NRG1 SNPS in 1304 patients with schizophrenia and 871 healthy controls. Then, 91 patients with schizophrenia and 40 healthy controls were selected to detect the peripheral plasma NRG1 immunoreactivity by ELISA. Among them, 84 patients were divided into rs6982890 genotypes to analyze the correlation between NRG1 immunoreactivity and clinical symptoms. RESULTS: Rs6982890 allelic frequencies were statistically significant between patients and controls. Baseline peripheral plasma NRG1 immunoreactivity in patients were significantly lower than controls. NRG1 immunoreactivity in patients were significantly increased after 8 weeks of antipsychotic treatment and significantly correlated with clinical symptoms and cognitive function. Genotyping of patients with SNP rs6982890 indicated NRG1 immunoreactivity in CC genotype increased significantly after treatment, while CT genotype had no significant change. Baseline NRG1 immunoreactivity with the CT genotype were significantly higher than CC genotype. CONCLUSIONS: NRG1 SNP rs6982890 is significantly associated with schizophrenia in the Han population of northern China, and it may affect the effect of antipsychotic drug treatment by regulating the peripheral plasma NRG1 immunoreactivity.
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Neurregulina-1 , Polimorfismo de Nucleótido Simple , Esquizofrenia , Humanos , Neurregulina-1/genética , Neurregulina-1/sangre , Esquizofrenia/genética , Esquizofrenia/sangre , Femenino , Masculino , Polimorfismo de Nucleótido Simple/genética , Adulto , Persona de Mediana Edad , China , Genotipo , Antipsicóticos/uso terapéutico , Predisposición Genética a la Enfermedad/genética , Frecuencia de los Genes , Trastornos Psicóticos/genética , Trastornos Psicóticos/sangre , Adulto JovenRESUMEN
Resistance to DNA-damaging agents is a major unsolved challenge for breast cancer patients undergoing chemotherapy. Here, we show that elevated expression of transcriptional repressor GATA binding 1 (TRPS1) is associated with lower drug sensitivity, reduced response rate, and poor prognosis in chemotherapy-treated breast cancer patients. Mechanistically, elevated TRPS1 expression promotes hyperactivity of DNA damage repair (DDR) in breast cancer cells. We provide evidence that TRPS1 dynamically localizes to DNA breaks in a Ku70-and Ku80-dependent manner and that TRPS1 is a new member of the DDR protein family. We also discover that the dynamics of TRPS1 assembly at DNA breaks is regulated by its reversible PARylation in the DDR, and that mutations of the PARylation sites on TRPS1 lead to increased sensitivity to chemotherapeutic drugs. Taken together, our findings provide new mechanistic insights into the DDR and chemoresistance in breast cancer patients and identify TRPS1 as a critical DDR protein. TRPS1 may also be considered as a target to improve chemo-sensitization strategies and, consequently, clinical outcomes for breast cancer patients.
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Neoplasias de la Mama , Reparación del ADN , Proteínas de Unión al ADN , Resistencia a Antineoplásicos , Proteínas Represoras , Humanos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Femenino , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Línea Celular Tumoral , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Factores de Transcripción GATA/metabolismo , Factores de Transcripción GATA/genética , Regulación Neoplásica de la Expresión Génica , Daño del ADNRESUMEN
The diagnostic value of liver biopsy has been confirmed in patients with abnormal liver test results; however, little data are available on its application in patients with portal hypertension. This study aimed to investigate the utility of liver biopsy for the etiological diagnosis of unexplained portal hypertension, and explore the clinical and pathological characteristics of each etiology. A retrospective observational analysis was conducted on 1367 patients who underwent liver biopsy at the Second Hospital of Nanjing from 2017 to 2019. Of these, 188 patients with unexplained portal hypertension were enrolled. The clinical and pathological characteristics were collected and reassessed in a multidisciplinary team meeting. Among these patients, 174 (92.6%, 174/188) had a definite etiological diagnosis through liver biopsy. The main etiologies were autoimmune hepatitis in 47 patients (25%, 47/188), autoimmune hepatitis-primary biliary cirrhosis overlap syndrome in 41 patients (21.8%, 41/188), and porto-sinusoidal vascular disease (PSVD) in 40 patients (21.3%, 40/188). Compared to liver cirrhosis, PSVD patients were younger and the liver function damage of which was subtler. The widths of portal vein diameter were widest in PSVD but the liver stiffness measurement were almost normal. Splenomegaly was common in PSVD, but ascites were less frequent than in autoimmune hepatitis (25.0% vs 51.1%, Pâ =â .013). Based on the histological patterns, we found that cholestatic liver diseases such as primary biliary cirrhosis, autoimmune hepatitis-primary biliary cirrhosis overlap syndrome, and progressive familial intrahepatic cholestasis could lead to non-cirrhotic portal hypertension, while vascular liver diseases such as PSVD and Budd-Chiari syndrome could also show fibrous proliferation as the disease progresses. Liver biopsy is safe and valuable for etiological diagnosis of unexplained portal hypertension. Cirrhosis is the leading cause of portal hypertension, and porto-sinusoidal vascular diseases should also be considered. Clinical features may be helpful in suggesting the cause; however, pathological examination is still indispensable for disease diagnosis and progression assessment.
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Hipertensión Portal , Hígado , Humanos , Hipertensión Portal/patología , Hipertensión Portal/diagnóstico , Hipertensión Portal/etiología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Biopsia/métodos , Hígado/patología , Adulto , Hepatitis Autoinmune/patología , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/complicaciones , Anciano , Cirrosis Hepática Biliar/patología , Cirrosis Hepática Biliar/diagnóstico , Cirrosis Hepática Biliar/complicaciones , Cirrosis Hepática/patología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/complicacionesRESUMEN
Autophagy is crucial for synaptic plasticity and the architecture of dendritic spines. However, the role of autophagy in schizophrenia (SCZ) and the mechanisms through which it affects synaptic function remain unclear. In this study, we identified 995 single nucleotide polymorphisms (SNPs) across 19 autophagy-related genes that are associated with SCZ. Gene Set Enrichment Analysis (GSEA) of data from the Gene Expression Omnibus public database revealed defective autophagy in patients with SCZ. Using a maternal immune activation (MIA) rat model, we observed that autophagy was downregulated during the weaning period, and early-life activation of autophagy with rapamycin restored abnormal behaviors and electrophysiological deficits in adult rats. Additionally, inhibition of autophagy with 3-Methyladenine (3-MA) during the weaning period resulted in aberrant behaviors, abnormal electrophysiology, increased spine density, and reduced microglia-mediated synaptic pruning. Furthermore, 3-MA treatment significantly decreased the expression and synaptosomal content of complement, impaired the recognition of C3b and CR3, indicating that autophagy deficiency disrupts complement-mediated synaptic pruning. Our findings provide evidence for a significant association between SCZ and defective autophagy, highlighting a previously underappreciated role of autophagy in regulating the synaptic and behavioral deficits induced by MIA.
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Autofagia , Plasticidad Neuronal , Ratas Sprague-Dawley , Destete , Animales , Autofagia/fisiología , Autofagia/efectos de los fármacos , Ratas , Plasticidad Neuronal/fisiología , Plasticidad Neuronal/efectos de los fármacos , Femenino , Masculino , Adenina/análogos & derivados , Adenina/farmacología , Humanos , Esquizofrenia/patología , Esquizofrenia/metabolismo , Esquizofrenia/genética , Proteínas del Sistema Complemento/metabolismo , Proteínas del Sistema Complemento/genética , Polimorfismo de Nucleótido Simple , Modelos Animales de Enfermedad , Sinapsis/patología , Sinapsis/metabolismo , Sinapsis/efectos de los fármacos , EmbarazoRESUMEN
OBJECTIVE: The role of Non-Alcoholic Fatty Liver Disease (NAFLD) on antiviral response in Chronic Hepatitis B (CHB) remains unclear. Previous studies mainly focus on the impact of the Non-Alcoholic Fatty Liver (NAFL) on antiviral efficacy, whereas the role of Non-Alcoholic Steatohepatitis (NASH) has not been highlighted. The authors aimed to investigate the association of NAFLD (NAFL and NASH), viral and histological characteristics with antiviral response. METHODS: The authors collected data of treatment-naïve CHB patients who underwent liver biopsy. All these patients received antiviral monotherapy and 48-week follow-up. The antiviral response was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the variables associated with antiviral response. RESULTS: Overall, 120 treatment-naïve CHB patients were enrolled, with 49.2 % (59/120) of them were complicated by NAFLD. Male (Odd Ratio [OR = 4.222], 95 % Confidence Interval [95 % CI 1.620-11.003]) and overweight (OR = 8.709, 95 % CI 3.355-22.606) were independent predictors for concurrent NAFLD. After 48-week follow-up, the authors found that the overall antiviral response did not differ between CHB patients with and without concomitant NAFL/NASH (p > 0.05). High viral load (Hazard Ratio [HR = 0.522], 95 % CI 0.286-0.952), advanced fibrosis (HR = 2.426, 95 % CI 1.256-4.686), and moderate-to-severe interface hepatitis (HR = 2.541, 95 % CI 1.406-4.592) were significantly correlated with antiviral response after 8-week follow-up. CONCLUSION: Neither NAFL nor NASH had an impact on antiviral therapy for CHB. It was low hepatitis B load, advanced fibrosis, and moderate-to-severe interface hepatitis that contributed to the virological response.
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Antivirales , Hepatitis B Crónica , Hígado , Enfermedad del Hígado Graso no Alcohólico , Humanos , Masculino , Enfermedad del Hígado Graso no Alcohólico/patología , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/patología , Femenino , Antivirales/uso terapéutico , Adulto , Biopsia , Persona de Mediana Edad , Hígado/patología , Resultado del Tratamiento , Carga Viral , Estimación de Kaplan-Meier , Estudios RetrospectivosRESUMEN
Habitual daytime napping is a common behavioral and lifestyle practice in particular countries and is often considered part of a normal daily routine. However, recent evidence suggests that the health effects of habitual daytime napping are controversial. We systematically searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to March 9, 2024, to synthesize cohort studies of napping and health outcome risk. A total of 44 cohort studies with 1,864,274 subjects aged 20-86 years (mean age 56.4 years) were included. Overall, habitual napping increased the risk of several adverse health outcomes, including all-cause mortality, cardiovascular disease, metabolic disease, and cancer, and decreased the risk of cognitive impairment and sarcopenia. Individuals with a napping duration of 30 min or longer exhibited a higher risk of all-cause mortality, cardiovascular disease, and metabolic disease, whereas those with napping durations less than 30 min had no significant risks. No significant differences in napping and health risks were observed for napping frequency, percentage of nappers, sample size, sex, age, body mass index, follow-up years, or comorbidity status. These findings indicate that individuals with a long napping duration should consider shortening their daily nap duration to 30 min or less.
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Background/Aims: Recent studies revealed that patients with persistent aminotransferase elevations after antiviral treatment had higher risk of hepatic events; yet its underlying causes remain unclear. Our study aimed to investigate the etiologies of persistent aminotransferase elevations in patients treated with nucleos(t)ide analogs (NAs). Materials and Methods: A retrospective study was conducted on chronic hepatitis B (CHB) patients who had been receiving NA treatment for over a year and had an aminotransferase level greater than 40 IU/mL (more than twice, with a 3-month interval) and subsequently underwent a liver biopsy. Results: The study group included 46 patients (34 males) with a mean age of 44.8 ± 20.3 years (range: 24-71 years).The average dura- tion of NA therapy was 3.7 years (1.1-10.6 years). The etiologies of persistant transaminase elevation were categorized into 4 groups: patients with low hepatitis B virus (HBV) viral load (LVL, n = 11); concurrent non-alcoholic fatty liver disease (NAFLD, n = 12); concurrent other liver diseases (OLD, n = 12); and unknown liver dysfunction (ULD, n = 11). The proportion of G ≥ 2 inflammation was significantly higher in the LVL group (90.9%) compared to NAFLD (33.3%), OLD (50%), and ULD (27.2%) groups (P = .012). The hepatitis B e-antigen (HBeAg)-positive group exhibited a younger age (34.5 ± 10.2 vs. 48.1 ± 9.4 years, P < .001), a lower proportion of fibrosis F ≥ 2 (36.3% vs. 77.1%, P = .012), and a higher prevalence of detectable HBV DNA (54.5% vs.14.2%, P = .00632) compared to the HBeAg-negative group. Conclusion: The etiology of persistent aminotransferase elevations in CHB patients undergoing NAs treatment warrants investigation. Besides the commonly observed NAFLD and low HBV viral load, concurrent presence of other liver diseases requires elucidation.The proportion of G≥2 inflammation was higher in the LVL group.
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Alanina Transaminasa , Antivirales , Hepatitis B Crónica , Carga Viral , Humanos , Masculino , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/sangre , Hepatitis B Crónica/virología , Femenino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Antivirales/uso terapéutico , Antivirales/efectos adversos , Anciano , Adulto Joven , Alanina Transaminasa/sangre , Virus de la Hepatitis B , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico , Nucleósidos/uso terapéuticoRESUMEN
Oxidative stress and neuroinflammation contribute to schizophrenia (SCZ) pathology and may influence treatment efficacy. Matrix metalloproteinase 9 (MMP9) is a critical molecular node mediating the interaction between oxidative stress and inflammation, and so may influence treatment efficacy. Here we examined the associations of plasma MMP9 concentration with antipsychotic drug responses, clinical symptoms, and brain structure. A total of 129 healthy controls and 124 patients with SCZ were included in this study. Patients were monitored clinically during 8 weeks of antipsychotic treatment and classified as poor responders (n = 49) or good responders (n = 75). We then compared plasma MMP9 concentrations in healthy controls at baseline and both SCZ responder groups at baseline and after the 8-week antipsychotic treatment regimen. Cognitive function was also examined using the MATRICS Consensus Cognitive Battery. In addition, we extracted regional white matter density from magnetic resonance images of patients. Compared to healthy controls, plasma MMP9 levels were significantly elevated in poor responders at baseline and negatively correlated with both white matter density in the right superior temporal gyrus and the change in cognitive symptoms after treatment. Conversely, there was no significant difference in plasma MMP9 between good responders and healthy controls, and no associations of plasma MMP9 with cognitive symptoms or regional white matter density among good responders. Elevated plasma MMP9 is associated with poor antipsychotic drug efficacy and white matter deficits in SCZ patients, and so may be a useful biomarker to guide personalized treatment.
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Processing is an indispensable technology in the preparation of Spirulina platensis (S. platensis). The key odorants in liquids, muds, and powders from S. platensis (NM and GZ) were characterized. A total of 90 odorants were identified and 41 odorants were sniffed with the flavor dilution (FD) factors ranging from 1 to 729. Among them, nonanal, decanal, d-limonene, ß-cyclocitral, and ß-ionone with FD factors ≥1 were detected in S. platensis during the whole processing stages. In addition, heptanal, (E, E)-2,4-nonadienal, trans-4,5-epoxy-(E)-2-decenal, 1-hepten-3-one, isophorone, 3-ethyl-2,5-dimethylpyrazine, and α-ionone exhibited higher odor activity values in powders; ß-myrcene, methional, and S-methyl methanethiosulphonate were key odorants in muds; while trans-3-penten-2-ol was key odorant in liquids. Besides, the GZ-mud presented stronger earthy and fishy odor than NM-mud. S. platensis powders have the stronger grassy odor, roasted odor, and marine odor than S. platensis muds. Overall, drying process promotes the formation of aldehydes, heterocyclic compounds, and terpenoids.
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Aromatizantes , Odorantes , Spirulina , Spirulina/química , Odorantes/análisis , Aromatizantes/química , Manipulación de Alimentos , Compuestos Orgánicos Volátiles/química , Cromatografía de Gases y Espectrometría de Masas , Humanos , Nariz ElectrónicaRESUMEN
UV-B radiation can induce the accumulation of many secondary metabolites, including flavonoids, in plants to protect them from oxidative damage. BRI1-EMS-SUPPRESSOR1 (BES1) has been shown to mediate the biosynthesis of flavonoids in response to UV-B. However, the detailed mechanism by which it acts still needs to be further elucidated. Here, we revealed that UV-B significantly inhibited the transcription of multiple transcription factor genes in tobacco, including NtMYB27, which was subsequently shown to be a repressor of flavonoids synthesis in tobacco. We further demonstrated that NtBES1 directly binds to the E-box motifs present in the promoter of NtMYB27 to mediate its transcriptional repression upon UV-B exposure. The UV-B-repressed NtMYB27 could bind to the ACCT-containing element (ACE) in the promoters of Nt4CL and NtCHS and served as a modulator that promoted the biosynthesis of lignin and chlorogenic acid (CGA) but inhibited the accumulation of flavonoids in tobacco. The expression of NtMYB27 was also significantly repressed by heat stress, suggesting its putative roles in regulating heat-induced flavonoids accumulation. Taken together, our results revealed the role of NtBES1 and NtMYB27 in regulating the synthesis of flavonoids during the plant response to UV-B radiation in tobacco.
RESUMEN
BACKGROUND AIMS: Studies have shown that blocking the PD-1/PD-L1 pathway may lead to a potential cure for HBV infections. ASC22 (Envafolimab) is a humanized, single-domain PD-L1 antibody administered subcutaneously. This study aimed to evaluate the efficacy and safety of ASC22 in virally suppressed chronic hepatitis B (CHB) patients on nucleos(t)ide analogs (NAs). APPROACH AND RESULTS: This randomized, single-blind, phase IIb trial enrolled CHB patients in two cohorts for a 24-week treatment with ASC22 or placebo (PBO) once every 2 weeks and 24-week follow-up. In total, 60, 59, and 30 patients were treated with 1.0, 2.5 mg/kg ASC22 and PBO, respectively. The mean HBsAg changes from baseline at week 24 and 24 week follow-up periods were -0.309 (p<0.001) and -0.272 (p<0.023) log10 IU/mL in the 1.0 mg/kg ASC22 group, -0.231 (p=0.007) and -0.205 (p=0.12) log10 IU/mL in the 2.5 mg/kg ASC22 group, and-0.003 and -0.063 log10 IU/mL in the PBO group, respectively (ITT population). Three out of ten patients with baseline HBsAg levels ≤100 IU/mL in the 1.0 mg/kg group obtained on-treatment HBsAg loss. Most AEs were mild (97.9%). There were no study drug-related serious AEs in the 1.0 mg/kg ASC22 group. CONCLUSIONS: Subcutaneous administration of 1.0 mg/kg ASC22 Q2W for 24 weeks was shown to be safe and well tolerated in virally suppressed CHB patients on NAs and can induce HBsAg decline, especially in patients with HBsAg ≤100 IU/mL.