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BACKGROUND AND AIM: Abdominal aortic calcification (AAC) is a key predictor of cardiovascular diseases (CVDs). The Oxidative Balance Score (OBS) served as a tool to evaluate the systemic status of oxidative stress. However, evidence on the link between OBS and severe abdominal aortic calcification (SAAC) is currently inadequate. This study aims to establish this correlation in the US adult population, contributing valuable insights to the understanding of cardiovascular health. METHODS AND RESULTS: In our study with 2745 participants from the 2013-2014 National Health and Nutrition Examination Survey (NHANES), we analyzed both OBS and AAC score data. Logistic regression and smooth curve fitting were used to investigate the relationship between OBS and SAAC. The overall prevalence of severe abdominal aortic calcification disease was 9.1%. Multivariable logistic regression revealed that higher oxidative balance scores were associated with a lower risk of SAAC. After adjusting for potential confounders (model III), for every 1-point increase in oxidative balance scores, the odds of SAAC decreased by 3% [OR = 0.97, 95% CI= (0.95,0.99), P = 0.03]. The dose-response relationship demonstrated a negative correlation between oxidative balance scores and SAAC (p for nonlinear = 0.368). CONCLUSIONS: This study reveals a negative association between oxidative balance scores and severe abdominal aortic calcification in US adults. The implications of these findings merit careful consideration and should be taken into account in the formulation of clinical guidelines and updates.
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OBJECTIVE: :Mass screening for human immunodeficiency virus (HIV) and preexposure prophylaxis (PrEP) may be effective measures for reducing the probability of HIV transmission. Our study aimed to determine the cost-effectiveness of preliminary screening in the general population, PrEP for HIV-negative spouses in serodiscordant couples, or both approaches in Zhejiang Province. DESIGN: :From a policy-maker's perspective, a Markov model was constructed to compare 4 strategies over a 30-year horizon. METHODS: :In the Markov model, the implementation intensities of the strategies varied from 50% to 100%. Different strategies were evaluated by the reduction of unfavorable clinical outcomes, saved life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and net monetary benefits (NMBs). RESULTS: :The PrEP-Screening strategy reduced the most unfavorable clinical outcomes and saved the most LYs and QALYs from 2023 to 2052. It always gained the maximum QALYs and NMB, while its ICER was always lower than the willingness-to-pay (WTP). The NMB of the PrEP-Screening strategy gradually increased as the implementation intensity increased. CONCLUSIONS: :With adequate manpower and policies, we suggest implementing the PrEP-Screening strategy in Zhejiang Province, suggesting that the broader the population coverage of the strategy, the better. In addition, the PrEP strategy is an alternative.
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OBJECTIVE: Temporal lobe epilepsy (TLE) patients often exhibit varying degrees of cognitive impairments. This study aims to predict cognitive performance in TLE patients by applying a connectome-based predictive model (CPM) to whole-brain resting-state functional connectivity (RSFC) data. METHODS: A CPM was established and leave-one-out cross-validation was employed to decode the cognitive performance of patients with TLE based on the whole-brain RSFC. RESULTS: Our findings indicate that cognitive performance in TLE can be predicted through the internal and network connections of the parietal lobe, limbic lobe, and cerebellum systems. These systems play crucial roles in cognitive control, emotion processing, and social perception and communication, respectively. In the subgroup analysis, CPM successfully predicted TLE patients with and without focal to bilateral tonic-clonic seizures (FBCTS). Additionally, significant differences were noted between the two TLE patient groups and the normal control group. CONCLUSION: This data-driven approach provides evidence for the potential of predicting brain features based on the inherent resting-state brain network organization. Our study offers an initial step towards an individualized prediction of cognitive performance in TLE patients, which may be beneficial for diagnosis, prognosis, and treatment planning.
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Conectoma , Epilepsia del Lóbulo Temporal , Imagen por Resonancia Magnética , Humanos , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/psicología , Masculino , Femenino , Conectoma/métodos , Adulto , Adulto Joven , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Cognición/fisiología , Persona de Mediana EdadRESUMEN
BACKGROUND: Vasculogenic mimicry, a novel neovascularization pattern of aggressive tumors, is associated with poor clinical outcomes. OBJECTIVE: The aim of this research was to establish a new model, termed VC score, to predict the prognosis, Tumor Microenvironment (TME) components, and immunotherapeutic response in Hepatocellular Carcinoma (HCC). METHODS: The expression data of the public databases were used to develop the prognostic model. Consensus clustering was performed to confirm the molecular subtypes with ideal clustering efficacy. The high- and low-risk groups were stratified utilizing the VC score. Various methodologies, including survival analysis, single-sample Gene Set Enrichment Analysis (ssGSEA), Tumor Immune Dysfunction and Exclusion scores (TIDE), Immunophenoscore (IPS), and nomogram, were utilized for verification of the model performance and to characterize the immune status of HCC tissues. GSEA was performed to mine functional pathway information. RESULTS: The survival and immune characteristics varied between the three molecular subtypes. A five-gene signature (TPX2, CDC20, CFHR4, SPP1, and NQO1) was verified to function as an independent predictive factor for the prognosis of patients with HCC. The high-risk group exhibited lower Overall Survival (OS) rates and higher mortality rates in comparison to the low-risk group. Patients in the low-risk group were predicted to benefit from immune checkpoint inhibitor therapy and exhibit increased sensitivity to immunotherapy. Enrichment analysis revealed that signaling pathways linked to the cell cycle and DNA replication processes exhibited enrichment in the high-risk group. CONCLUSIONS: The VC score holds the potential to establish individualized treatment plans and clinical management strategies for patients with HCC.
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Digestive system tumors have been reported in more than 25% of all cancer cases worldwide, bringing a huge burden on the healthcare system. RNA methylation modification-an important post-transcriptional modification-has become an active research area in gene regulation. It is a dynamic and reversible process involving several enzymes, such as methyltransferases, demethylases, and methylation reader proteins. This review provides insights into the role of three major methylation modifications, namely m6A, m5C, and m1A, in the development of digestive system tumors, specifically in the development of tumor immune microenvironment (TIME) of these malignancies. Abnormal methylation modification affects immunosuppression and antitumor immune response by regulating the recruitment of immune cells and the release of immune factors. Understanding the mechanisms by which RNA methylation regulates digestive system tumors will be helpful in exploring new therapeutic targets.
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Neoplasias del Sistema Digestivo , Neoplasias Gastrointestinales , Humanos , Metilación de ARN , Neoplasias del Sistema Digestivo/genética , Metiltransferasas , Procesamiento Proteico-Postraduccional , Microambiente Tumoral , ARNRESUMEN
Background: Aging is an important factor in the development of Alzheimer's disease (AD). The senescent cells can be recognized and removed by NK cells. However, NK cell function is gradually inactivated with age. Therefore, this study used senescence as an entry point to investigate how NK cells affect AD. Methods: The study validated the correlation between cognition and aging through a prospective cohort of the National Health and Nutrition Examination Survey database. A cellular trajectory analysis of the aging population was performed using single-cell nuclear transcriptome sequencing data from patients with AD and different ages. The genome-wide association study (GWAS) cohort of AD patients was used as the outcome event, and the expression quantitative trait locus was used as an instrumental variable. Causal associations between genes and AD were analyzed by bidirectional Mendelian randomization (MR) and co-localization. Finally, clinical cohorts were constructed to validate the expression of key genes. Results: A correlation between cognition and aging was demonstrated using 2,171 older adults over 60 years of age. Gene regulation analysis revealed that most of the highly active transcription factors were concentrated in the NK cell subpopulation of AD. NK cell trajectories were constructed for different age populations. MR and co-localization analyses revealed that CHD6 may be one of the factors influencing AD. Conclusion: We explored different levels of AD and aging from population cohorts, single-cell data, and GWAS cohorts and found that there may be some correlations of NK cells between aging and AD. It also provides some basis for potential causation.
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Enfermedad de Alzheimer , Humanos , Persona de Mediana Edad , Anciano , Enfermedad de Alzheimer/genética , Estudio de Asociación del Genoma Completo , Encuestas Nutricionales , Estudios Prospectivos , Perfilación de la Expresión Génica , Envejecimiento/genética , Células Asesinas Naturales , ADN Helicasas , Proteínas del Tejido NerviosoRESUMEN
BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia. The ratio of red cell distribution width (RDW) to albumin has been recognized as a reliable prognostic marker for poor outcomes in a variety of diseases. However, the evidence regarding the association between RDW to albumin ratio (RAR) and in hospital mortality in patients with AF admitted to the Intensive Care Unit (ICU) currently was unclear. The purpose of this study was to explore the association between RAR and in hospital mortality in patients with AF in the ICU. METHODS: This retrospective cohort study used data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database for the identification of patients with atrial fibrillation (AF). The primary endpoint investigated was in-hospital mortality. Multivariable-adjusted Cox regression analysis and forest plots were utilized to evaluate the correlation between the RAR and in-hospital mortality among patients with AF admitted to ICU. Additionally, receiver operating characteristic (ROC) curves were conducted to assess and compare the predictive efficacy of RDW and the RAR. RESULTS: Our study included 4,584 patients with AF with a mean age of 75.1 ± 12.3 years, 57% of whom were male. The in-hospital mortality was 20.3%. The relationship between RAR and in-hospital mortality was linear. The Cox proportional hazard model, adjusted for potential confounders, found a high RAR independently associated with in hospital mortality. For each increase of 1 unit in RAR, there is a 12% rise in the in-hospital mortality rate (95% CI 1.06-1.19). The ROC curves revealed that the discriminatory ability of the RAR was better than that of RDW. The area under the ROC curves (AUCs) for RAR and RDW were 0.651 (95%CI: 0.631-0.671) and 0.599 (95% CI: 0.579-0.620). CONCLUSIONS: RAR is independently correlated with in hospital mortality and in AF. High level of RAR is associated with increased in-hospital mortality rates.
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Fibrilación Atrial , Índices de Eritrocitos , Humanos , Masculino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Fibrilación Atrial/diagnóstico , Mortalidad Hospitalaria , Estudios Retrospectivos , Cuidados Críticos , PronósticoRESUMEN
Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. Since the tricarboxylic acid cycle is widely involved in tumor metabolic reprogramming and cuproptosis, investigating related genes may help to identify prognostic signature of patients with HCC. Data on patients with HCC were sourced from public datasets, and were divided into train, test, and single-cell cohorts. A variety of machine learning algorithms were used to identify different molecular subtypes and determine the prognostic risk model. Our findings revealed that the risk score (TRscore), based on the genes OGDHL, CFHR4, and SPP1, showed excellent predictive performance in different datasets. Pathways related to cell cycle and immune inflammation were enriched in the high-risk group, whereas metabolism-related pathways were significantly enriched in the low-risk group. The high-risk group was associated with a greater number of mutations of detrimental biological behavior and higher levels of immune infiltration, immune checkpoint expression, and anti-cancer immunotherapy response. Low-risk patients demonstrated greater sensitivity to erlotinib and phenformin. SPP1 was mainly involved in the interaction among tumor-associated macrophages, T cells, and malignant cells via SPP1-CD44 and SPP1-(ITGA5 + ITGB1) ligand-receptor pairs. In summary, our study established a prognostic model, which may contribute to individualized treatment and clinical management of patients with HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Pronóstico , Ciclo del Ácido Cítrico/genética , Neoplasias Hepáticas/genética , Algoritmos , Microambiente TumoralRESUMEN
Nocardia pseudobrasiliensis is a new taxon constituting an emerging species of human pathogenic Nocardia, which shares morphological features with N. brasiliensis. However, N. pseudobrasiliensis is more invasive and more easily disseminated, and it exhibits distinctive antibiotic susceptibility. Few clinical cases related to N. pseudobrasiliensis infection have been reported, and N. pseudobrasiliensis hydrarthrosis has not been described. Here, we analyzed the case information, diagnostic process, treatment, and prognosis of a patient with N. pseudobrasiliensis hydrarthrosis who received treatment in Zhejiang Provincial People's Hospital. Magnetic resonance imaging showed joint cavity effusion and soft tissue swelling with high signal on proton density-fat saturated images and low signal on T1-weighted images. Oil microscopy revealed abundant acid-fast-positive filaments in hydrarthrosis puncture fluid. The pathogen was identified as N. pseudobrasiliensis by matrix-assisted laser desorption ionization-time of flight mass spectrometry. In contrast to the 100% ciprofloxacin resistance displayed by N. brasiliensis, this clinical isolate of N. pseudobrasiliensis was completely susceptible. In summary, this is the first report of N. pseudobrasiliensis in joint effusion from a patient with arthritis.
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Artritis , Hidrartrosis , Nocardiosis , Nocardia , Humanos , Nocardiosis/complicaciones , Nocardiosis/diagnóstico , Nocardiosis/tratamiento farmacológicoRESUMEN
Objectives: The aim of this article was to compare the differences between Intergrowth-21st (IG-21) and Fenton growth standards in the classification of intrauterine and extrauterine growth restriction (EUGR) in eastern Chinese preterm infants, and detect which one can better relate to neonatal diseases and predict the physical growth outcomes at 3-5 years old. Methods: Premature infants admitted to a tertiary pediatric hospital in Shanghai, China, from 2016 to 2018 were enrolled. Prenatal information, neonatal diseases during hospitalization, and anthropometric data (weight, height, and head circumference) at birth and at discharge were collected and analyzed. Physical growth outcomes (short stature, thinness, and overweight) were examined by telephone investigations in 2021 at age 3-5 years. Results: The medium gestational age and birth weight of the included 1,065 preterm newborns were 33.6â weeks and 1,900â g, respectively. The IG-21 curves diagnosed more newborns with small for gestational age (SGA) (19% vs. 14.7%) and fewer newborns with longitudinal EUGR on height (25.5% vs. 27.9%) and head circumference (17.9% vs. 24.7%) compared to Fenton curves. Concordances between Fenton and IG-21 standards were substantial or almost perfect in the classification of SGA and longitudinal EUGR, but minor in cross-sectional EUGR. EUGR identified by Fenton curves was better related to neonatal diseases than IG-21 curves. There were no statistical significances in the prediction of short stature, thinness, and overweight at 3-5 years old between the two charts. Conclusions: IG-21 growth standards are not superior to Fenton in assessing preterm growth and development in the eastern Chinese population.
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BACKGROUND: Our study aimed to compare the predictive performance of different hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B patients receiving entecavir or tenofovir, including discrimination, calibration, negative predictive value (NPV) in low-risk, and proportion of low-risk. METHODS: We conducted a systematic literature research in PubMed, EMbase, the Cochrane Library, and Web of Science before January 13, 2022. The predictive performance was assessed by area under receiver operating characteristic curve (AUROC), calibration index, negative predictive value, and the proportion in low-risk. Subgroup and meta-regression analyses of discrimination and calibration were conducted. Sensitivity analysis was conducted to validate the stability of the results. RESULTS: We identified ten prediction models in 23 studies. The pooled 3-, 5-, and 10-year AUROC varied from 0.72 to 0.84, 0.74 to 0.83, and 0.76 to 0.86, respectively. REAL-B, AASL-HCC, and HCC-RESCUE achieved the best discrimination. HCC-RESCUE, PAGE-B, and mPAGE-B overestimated HCC development, whereas mREACH-B, AASL-HCC, REAL-B, CAMD, CAGE-B, SAGE-B, and aMAP underestimated it. All models were able to identify people with a low risk of HCC accurately. HCC-RESCUE and aMAP recognized over half of the population as low-risk. Subgroup analysis and sensitivity analysis showed similar results. CONCLUSION: Considering the predictive performance of all four aspects, we suggest that HCC-RESCUE was the best model to utilize in clinical practice, especially in primary care and low-income areas. To confirm our findings, further validation studies with the above four components were required.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Tenofovir/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/epidemiología , Neoplasias Hepáticas/epidemiología , Antivirales/uso terapéuticoRESUMEN
Lignocellulosic biomass (LCB) has been recognized as a valuable carbon source for the sustainable production of biofuels and value-added biochemicals. Crude enzymes produced by fungal cell factories benefit economic LCB degradation. However, high enzyme production cost remains a great challenge. Filamentous fungi have been widely used to produce cellulolytic enzymes. Metabolic engineering of fungi contributes to efficient cellulase production for LCB biorefinery. Here the latest progress in utilizing fungal cell factories for cellulase production was summarized, including developing genome engineering tools to improve the efficiency of fungal cell factories, manipulating promoters, and modulating transcription factors. Multi-omics analysis of fungi contributes to identifying novel genetic elements for enhancing cellulase production. Furthermore, the importance of translation regulation of cellulase production are emphasized. Efficient development of fungal cell factories based on integrative strain engineering would benefit the overall bioconversion efficacy of LCB for sustainable bioproduction.
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Celulasa , Celulasa/metabolismo , Hongos/metabolismo , Lignina/metabolismo , Ingeniería Metabólica , Biomasa , BiocombustiblesRESUMEN
Methods: We retrospectively screened individuals with serum Cp ≥ 140 mg/L from 1032 WD patients who were hospitalised for the first time. Logistic regression analyses were performed in a case-control study between the WD cohort and another liver disease cohort to explore the independent risk factors for WD diagnosis and establish a regression model to identify them. The follow-up medical records of the WD cohort were subjected to mixed-effects model analysis in a longitudinal study to discover factors associated with Cp normalisation. Results: Eighty-six WD patients and their 353 medical records and another 98 non-WD liver disease patients were included in the present study. Cp normalisation was significantly associated with the copper burden and liver function indexes, such as urinary copper, γ-glutamyltransferase, and albumin (p ≤ 0.001). Logistic regression analysis showed that age and serum creatinine (p ≤ 0.001) were independent risk factors associated with WD. The AUC value of the regression model in the total cohort was 0.926 (p ≤ 0.001). At a cutoff value of ≥0.617 and ≥-1, the positive and negative predictive values were both 90.8% for WD. Conclusion: Increased serum Cp in WD patients is related to excessive copper burden and hepatic injury, and common tests can effectively distinguish WD patients from other liver injury patients.
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Degeneración Hepatolenticular , Humanos , Degeneración Hepatolenticular/diagnóstico , Degeneración Hepatolenticular/complicaciones , Ceruloplasmina/análisis , Ceruloplasmina/metabolismo , Cobre/metabolismo , Creatinina , Estudios Retrospectivos , Estudios de Casos y Controles , Estudios LongitudinalesRESUMEN
Background: Nocardia cyriacigeorgica, which mainly causes pleuropulmonary and disseminated nocardiosis, has been proved to be one of the most common opportunistic pathogens in patients with immunodeficiency, but the cases that cause subcutaneous abscesses in normal individuals are rare and should be paid attention to. Methods: The clinical data of a patient with cutaneous nocardiosis caused by Nocardia cyriacigeorgica in Zhejiang Provincial People's Hospital were retrospectively analyzed, including clinical manifestations, laboratory examinations, imaging examinations, medication and prognosis. Results: Magnetic resonance imaging (MRI) showed that there was a 26 mm × 73 mm abscess under the skin. The pus in the abscess was green. Gram staining showed positive branched rod-shaped and undivided hyphae. After culture, small wrinkle dry white small colonies were observed, and it was identified as Nocardia cyriacigeorgica by MALDI-TOF MS. Conclusion: We report the first case of a subcutaneous abscess caused by Nocardia cyriacigeorgica in an immunocompetent patient. Compared with cutaneous nocardiosis of which approximately 80% caused by Nocardia brasiliensis invasion, infection of Nocardia cyriacigeorgica is more insidious and latent, the features of the lesions are also unique. For this Nocardia cyriacigeorgica clinical isolate, the tested antibacterial drugs are generally sensitive and have an ideal prognosis after treatment with linezolid and timely debridement.
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We analyzed the clinical characteristics and outcomes of patients with Streptococcus suis meningitis in Liuzhou, China, to improve diagnostic accuracy and lower the chances of misdiagnosis. The major clinical manifestations, auxiliary examination results, treatment strategies, treatment efficacy, and follow-up results of 17 consecutively admitted patients with S. suis meningitis were evaluated. The most common clinical manifestations were fever (15/17), sensorineural hearing loss (13/17), headache (11/17), and altered mental status (8/17). In addition, 64.71% of the patients had residual symptoms of sensorineural hearing loss at discharge, and moderate disabilities occurred in 68.75% of the patients in the form of sensorineural deafness (11/17) and hemiparesis (1/17). The cerebrospinal fluid (CSF) of nine patients was used for metagenomic analysis with next-generation sequencing. The metagenomic analysis of CSF of four patients was positive, whereas blood and CSF cultures were negative. The average modified Rankin Scale (mRS) and Activities of Daily Living (ADL) scores improved significantly at the 6-month follow-up compared with those at admission (P < 0.05). There was no correlation between altered mRS and ADL scores and the CSF findings (P > 0.05). Early administration of antibiotics can prevent sensorineural hearing loss. Early CSF metagenomic analysis may be superior to blood and CSF culture.
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Pérdida Auditiva Sensorineural , Meningitis Bacterianas , Infecciones Estreptocócicas , Streptococcus suis , Humanos , Estudios de Seguimiento , Actividades Cotidianas , Infecciones Estreptocócicas/diagnóstico , ChinaRESUMEN
BACKGROUND: The primary aim of the study was to assess the nutritional status of pediatric liver transplant outpatients in nutrition clinic, particularly the nutritional status of their bones. METHODS: One hundred thirty-eight pediatric liver transplant outpatients, who had visited the nutrition clinic in Shanghai Children's Medical Center between January 2017 and December 2019, were recruited. The bone mineral density (BMD) z-scores were determined by dual energy X-ray absorptiometry (DXA). Nutritional assessment was performed, and their corresponding height-for-age z-scores (HAZs)/weight-for-age z-scores (WAZs)/BMI-for-age z-scores (BMIZs) were obtained. RESULTS: A total of 138 patients came to our nutrition outpatient clinic, including 68 boys (49.3%) and 70 girls (50.7%). The median age was 0.87y (0.68y, 1.71y). Among these patients, 44 (31.9%) had acute malnutrition with WAZ/BMIZ value -1.14 (-2.38, -0.18), 55 (38.4%) had chronic malnutrition with HAZ value -1.51 (-2.39, -0.38), and 96 (69.6%) had a BMD lower than normal. The BMD z-score was significantly correlated with the WAZ/BMIZ value (Spearman's correlation coefficient = 0.334, p < 0.001). A total of 37 infants re-visited the nutrition clinic for a follow-up after (147 ± 127) days. The WAZ/BMIZ value of the re-visiting patients and the BMD z-score of the re-visiting patients were significantly improved compared to those of the first-visit patients (p = 0.004 and p = 0.001 respectively). CONCLUSIONS: There were different rates of malnutrition before and after liver transplantation. At the same time, BMD Z-score and serum vitamin D level of patients decreased. There was a significant correlation between BMD z-scores and WAZ/BMIZ values. Proper and professional nutrition guidance significantly improved the WAZ/BMIZ-values and BMD Z-score of liver transplantation patients.
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Trasplante de Hígado , Desnutrición , Masculino , Femenino , Niño , Humanos , Lactante , Densidad Ósea , Estudios Retrospectivos , Incidencia , China/epidemiología , Absorciometría de Fotón , Desnutrición/diagnóstico , Desnutrición/epidemiología , HospitalesRESUMEN
Background: This study is aimed at investigating whether relaxin-3 exhibits protective effects against cardiomyopathy in diabetic rats by suppressing ERS. Methods: Eighty male SD rats were randomly divided into two groups: controls (n = 20) and diabetes (n = 60). The streptozotocin-treated rats were randomly divided into three groups: diabetic group (DM), low-dose relaxin-3 group (0.2 µg/kg/d), and high-dose relaxin-3 group (2 µg/kg/d). The myocardial tissues and collagen fiber were observed by hematoxylin and eosin (H&E) and Masson staining. Serum brain natriuretic peptide (BNP), troponin (TNI), myoglobin, interleukin (IL-17), interleukin (IL)-1α, and tumor necrosis factor (TNF)-α were determined by ELISA. The protein expression of glucose regulatory protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the heart tissue of each group was detected by Western blot analysis. Results: (1) HE and Masson staining indicated that relaxin-3 could attenuate myocardial lesions and myocardial collagen volume fraction. (2) BNP, TnI, and myoglobin in the DM group at four and eight weeks were significantly higher than in the controls (P < 0.01). The relaxin-3-treated groups showed significantly reduced serum BNP, TnI, and myoglobin levels compared with the DM group (P < 0.05). (3) IL-17, IL-1α, and TNF-α levels in the DM rats at 4 weeks were higher than in the controls (P < 0.05). Low or high dose of relaxin-3-treated groups showed reduced serum IL-17 and TNF-α levels compared with the DM group at four and eight weeks (P < 0.05). (4) CHOP and GRP78 protein expression was increased in the DM group at four and eight weeks compared with the controls (P < 0.01), and small and large doses of relaxin-3 significantly reduced GRP78 and CHOP protein expression. Conclusions: Exogenous relaxin-3 ameliorates diabetic cardiomyopathy by inhibiting ERS in diabetic rats.
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Diabetes Mellitus Experimental , Cardiomiopatías Diabéticas , Relaxina , Animales , Apoptosis , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Cardiomiopatías Diabéticas/tratamiento farmacológico , Cardiomiopatías Diabéticas/patología , Estrés del Retículo Endoplásmico , Eosina Amarillenta-(YS)/farmacología , Eosina Amarillenta-(YS)/uso terapéutico , Glucosa , Hematoxilina/farmacología , Hematoxilina/uso terapéutico , Interleucina-17/farmacología , Interleucina-17/uso terapéutico , Masculino , Mioglobina/farmacología , Mioglobina/uso terapéutico , Péptido Natriurético Encefálico/farmacología , Péptido Natriurético Encefálico/uso terapéutico , Ratas , Ratas Sprague-Dawley , Relaxina/farmacología , Relaxina/uso terapéutico , Estreptozocina/farmacología , Estreptozocina/uso terapéutico , Troponina/farmacología , Troponina/uso terapéutico , Factor de Necrosis Tumoral alfaRESUMEN
OBJECTIVE: In the present systematic review and meta-analysis, we sought to compare the efficacy and safety of tirofiban administered in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT) with or without mechanical thrombectomy (MT). METHODS: We searched PubMed, Web of Science, Embase and the Cochrane Library for randomized clinical trials and observational studies published between 2001 and 2021 that provided outcomes of AIS patients who underwent IVT alone or IVT bridging with or without tirofiban. The primary outcome was the proportion of patients achieving a modified Rankin Scale (mRS) score of 0-2 at 90 days. The secondary outcomes included the rates of (1) an excellent outcome defined as a mRS score of 0 or 1 at 90 days, (2) any type of intracranial hemorrhage (ICH), (3) symptomatic intracranial hemorrhage (sICH), (4) mortality, and (5) successful recanalization. RESULTS: We included 722 patients with IVT bridging therapy in 3 trials; there were 171 patients in the tirofiban group and 551 patients in the nontirofiban group. We included 846 patients with IVT alone in 7 studies; there were 471 patients in the tirofiban group and 375 patients in the nontirofiban group. The patients treated with tirofiban had a reduced risk of mortality compared to the patients treated without tirofiban during IVT bridging (OR, 0.46; 95 % CI, 0.24-0.89; p = 0.02), but no significant differences were found in safety outcomes on sICH, ICH, recanalization or efficacy outcomes on modified Rankin scale 0-2 (p > 0.05). Pooled results showed that tirofiban combined with IVT alone did not increase the risks of sICH, ICH or mortality but was significantly associated with excellent (OR, 2.68; 95 % CI, 1.58-4.55; P = 0.0003) and favorable (OR, 2.36; 95 % CI, 1.58-3.52; p < 0.0001) functional outcomes at 90 days. CONCLUSION: In AIS patients who underwent IVT or bridging therapy, early administration of tirofiban may be effective and safe, but further studies are needed to confirm the efficacy.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Tirofibán/uso terapéutico , Tirofibán/efectos adversos , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/complicaciones , Trombectomía/métodos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular/complicaciones , Resultado del Tratamiento , Terapia Trombolítica/métodos , Hemorragias Intracraneales/etiología , Administración Intravenosa , FibrinolíticosRESUMEN
We studied longitudinal changes in the microbiome with weight gain during atypical antipsychotics (APs) treatment. 43 inpatients naive to AP paediatric medication were included in the longitudinal microbiota study. The baseline composition of the gut microbiome in the case group was characterised by an increase in Parabacteroides and Eubacterium_hallii_group. During the follow-up, the relative abundances of Romboutsia and Klebsiella increased significantly after 3 months of AP treatment; however, no significant changes in these two gut bacteria were observed in the control group. The baseline composition of the gut microbiome contributed to the risk of AP-associated weight gain.
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Antipsicóticos , Microbioma Gastrointestinal , Antipsicóticos/efectos adversos , Niño , Humanos , Estudios Longitudinales , Proyectos Piloto , Aumento de PesoRESUMEN
Objectives: To investigate the postnatal growth trajectories of preterm infants and evaluate the association between extrauterine growth restriction (EUGR) at discharge and adverse physical growth outcomes at age 3-6 years. Methods: Premature infants admitted to Shanghai Children's Medical Center within 24 h after birth from 1 January 2016 to 31 December 2018 were enrolled. Neonatal complications, nutrition support, and anthropometric data were collected and analyzed to diagnose EUGR on different definitions at discharge. The weight and the height of each subject were collected by telephone investigation from 1 September 2021 to 31 November 2021 to access the incidences of overweight/obesity, short stature, and thinness at age 3-6 years. Results: A total of 527 preterm infants were included in the final sample. The overall mean weight and height Z-scores were -0.37 ± 0.97 SD and -0.29 ± 1.18 SD at birth, and increased to -0.03 ± 1.11 SD and 0.13 ± 1.2 SD at follow-up, respectively. The logistic regression analysis indicated longitudinal EUGR on head circumference as the risk factor of overweight or obesity, cross-sectional EUGR on height as the risk factor of short stature, and delayed EN as the risk factor of thinness. Conclusion: The growth trajectories of the preterm newborns tended toward the normal direction. Longitudinal EUGR on the head circumference and cross-sectional EUGR on height at discharge were associated with adverse physical growth outcomes at age 3-6 years.