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Background: Glycosyltransferase-associated genes play a crucial role in hepatocellular carcinoma (HCC) pathogenesis. This study investigates their impact on the tumor microenvironment and molecular mechanisms, offering insights into innovative immunotherapeutic strategies for HCC. Methods: We utilized cutting-edge single-cell and spatial transcriptomics to examine HCC heterogeneity. Four single-cell scoring techniques were employed to evaluate glycosyltransferase genes. Spatial transcriptomic findings were validated, and bulk RNA-seq analysis was conducted to identify prognostic glycosyltransferase-related genes and potential immunotherapeutic targets. MGAT1's role was further explored through various functional assays. Results: Our analysis revealed diverse cell subpopulations in HCC with distinct glycosyltransferase gene activities, particularly in macrophages. Key glycosyltransferase genes specific to macrophages were identified. Temporal analysis illustrated macrophage evolution during tumor progression, while spatial transcriptomics highlighted reduced expression of these genes in core tumor macrophages. Integrating scRNA-seq, bulk RNA-seq, and spatial transcriptomics, MGAT1 emerged as a promising therapeutic target, showing significant potential in HCC immunotherapy. Conclusion: This comprehensive study delves into glycosyltransferase-associated genes in HCC, elucidating their critical roles in cellular dynamics and immune cell interactions. Our findings open new avenues for immunotherapeutic interventions and personalized HCC management, pushing the boundaries of HCC immunotherapy.
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Carcinoma Hepatocelular , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , N-Acetilglucosaminiltransferases , Análise de Célula Única , Transcriptoma , Microambiente Tumoral , Animais , Humanos , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/imunologia , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Glicosiltransferases/genética , Imunoterapia/métodos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , N-Acetilglucosaminiltransferases/genética , N-Acetilglucosaminiltransferases/metabolismoRESUMO
BACKGROUND: A high-flow nasal cannula (cHFNC) delivers flow continuously (during inspiration and expiration). Using the diaphragm electrical activity (Edi), synchronizing HFNC could be an alternative (cycling high/low flow on inspiration/expiration, respectively). The objective of this study was to demonstrate the feasibility of synchronized HFNC (sHFNC) and compare it to cHFNC. METHODS: Different levels of cHFNC and sHFNC (4, 6, 8, and 10 liters per minute [LPM], with 2 LPM on expiration for sHFNC) were compared in eight rabbits (mean weight 3.16 kg), before and after acute lung injury (pre-ALI and post-ALI). Edi, tracheal pressure (Ptr), esophageal pressure (Pes), flow, and arterial CO2 were measured. In addition to the animal study, one 3.52 kg infant received sHFNC and cHFNC using a Servo-U ventilator. RESULTS: In the animal study, there were more pronounced decreases in Edi, reduced Pes swings and reduced PaCO2 at comparable flows during sHFNC compared to cHFNC both pre and post-ALI (p < .05). Baseline (pre-inspiratory) Ptr was 2-7 cmH2O greater during cHFNC (p < .05) indicating more dynamic hyperinflation. In one infant, the ventilator performed as expected, delivering Edi-synchronized high/low flow. CONCLUSION: Synchronizing high flow unloaded breathing, decreased Edi, and reduced PaCO2 in an animal model and is feasible in infants.
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BACKGROUND: Severe acute lung failure (ALF) often necessitates veno-venous extracorporeal membrane oxygenation (VV-ECMO), where identifying predictors of weaning success and mortality remains crucial yet challenging. The study aims to identify predictors of weaning success and mortality in adults undergoing VV-ECMO for severe ALF, a gap in current clinical knowledge. METHODS AND ANALYSIS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials will be searched for cohort studies examining the predictive factors of successful weaning and mortality in adult patients on VV-ECMO due to severe ALF. Risk of bias assessment will be conducted using the Newcastle-Ottawa scale for each included study. The primary outcomes will be successful weaning from VV-ECMO and all-cause mortality. Between-study heterogeneity will be evaluated using the I2 statistic. Sensitivity, subgroup, and meta-regression analyses will be performed to ascertain potential sources of heterogeneity and assess the robustness of our results. We will use the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool to recommend the level of evidence. DISCUSSION: This study seeks to provide clinically significant insights into predictors for weaning and mortality during VV-ECMO treatment for ALF, aiming to support clinical decisions and potentially influence health policy, thereby improving patient outcomes. ETHICS AND DISSEMINATION: Given the absence of direct engagement with human subjects or access to personal medical records, ethical approval for this study is deemed unnecessary. The study findings will be shared at a scientific conference either at the global or national level. Alternatively, the results will be presented for publication in a rigorously peer-reviewed journal regarding critical care medicine.
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Lesão Pulmonar Aguda , Oxigenação por Membrana Extracorpórea , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Adulto , Lesão Pulmonar Aguda/terapia , Lesão Pulmonar Aguda/mortalidade , Estudos de CoortesRESUMO
Endothelial dysfunction is associated with the progression of sepsis. This study sought to probe the molecular route of sex-determining region on the Y chromosome-box transcription factor 18 (SOX18) in sepsis-associated endothelial injury. Human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) to establish the sepsis cell model. Cell viability, lactate dehydrogenase (LDH) release, oxidative stress (reactive oxygen species/malondialdehyde/superoxide dismutase), and inflammation (interleukin-1ß/tumor necrosis factor-α/interleukin-6) were evaluated by cell counting kit-8 assay and relevant assay kits. The expression levels of SOX18, microRNA (miR)-204-5p, and cadherin-2 (CDH2) in cells were determined by real-time quantitative polymerase chain reaction and Western blot assay. The interaction of SOX18, miR-204-5p, and CDH2 was analyzed by chromatin immunoprecipitation and dual-luciferase assay. LPS induced HUVECs injury and downregulation of SOX18. SOX18 overexpression increased cell viability, while decreased LDH activity, oxidative stress, and inflammation. SOX18 bound to the miR-204-5p promoter to promote miR-204-5p expression, and further repressed CDH2 expression. miR-204-5p knockdown and CDH2 overexpression abrogated the protective role of SOX18 in HUVECs injury. Overall, SOX18 alleviated LPS-induced injury of HUVECs by promoting miR-204-5p and repressing CDH2, suggesting it as a potential target for sepsis treatment.
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MicroRNAs , Sepse , Humanos , Células Endoteliais da Veia Umbilical Humana , Lipopolissacarídeos , Inflamação , MicroRNAs/genética , Fatores de Transcrição SOXF/genéticaRESUMO
BACKGROUND: Mechanical ventilation is applied to unload the respiratory muscles, but knowledge about transpulmonary driving pressure (ΔPL) is important to minimize lung injury. We propose a method to estimate ΔPL during neurally synchronized assisted ventilation, with a simple intervention of lowering the assist for one breath ("lower assist maneuver", LAM). METHODS: In 24 rabbits breathing spontaneously with imposed loads, titrations of increasing assist were performed, with two neurally synchronized modes: neurally adjusted ventilatory assist (NAVA) and neurally triggered pressure support (NPS). Two single LAM breaths (not sequentially, but independently) were performed at each level of assist by acutely setting the assist to zero cm H2O (NPS) or NAVA level 0 cm H2O/uV (NAVA) for one breath. NPS and NAVA titrations were followed by titrations in controlled-modes (volume control, VC and pressure control, PC), under neuro-muscular blockade. Breaths from the NAVA/NPS titrations were matched (for flow and volume) to VC or PC. Throughout all runs, we measured diaphragm electrical activity (Edi) and esophageal pressure (PES). We measured ΔPL during the spontaneous modes (PL_PES) and controlled mechanical ventilation (CMV) modes (PL_CMV) with the esophageal balloon. From the LAMs, we derived an estimation of ΔPL ("PL_LAM") using a correction factor (ratio of volume during the LAM and volume during assist) and compared it to measured ΔPL during passive (VC or PC) and spontaneous breathing (NAVA or NPS). A requirement for the LAM was similar Edi to the assisted breath. RESULTS: All animals successfully underwent titrations and LAMs for NPS/NAVA. One thousand seven-hundred ninety-two (1792) breaths were matched to passive ventilation titrations (matched Vt, r = 0.99). PL_LAM demonstrated strong correlation with PL_CMV (r = 0.83), and PL_PES (r = 0.77). Bland-Altman analysis revealed little difference between the predicted PL_LAM and measured PL_CMV (Bias = 0.49 cm H2O and 1.96SD = 3.09 cm H2O). For PL_PES, the bias was 2.2 cm H2O and 1.96SD was 3.4 cm H2O. Analysis of Edi and PES at peak Edi showed progressively increasing uncoupling with increasing assist. CONCLUSION: During synchronized mechanical ventilation, a LAM breath allows for estimations of transpulmonary driving pressure, without measuring PES, and follows a mathematical transfer function to describe respiratory muscle unloading during synchronized assist.
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Infecções por Citomegalovirus , Suporte Ventilatório Interativo , Animais , Coelhos , Respiração Artificial , Respiração com Pressão Positiva , RespiraçãoRESUMO
Objective: Weaning failure is associated with adverse clinical outcomes. This study aimed to evaluate the accuracy of pendelluft during the spontaneous breathing trials (SBT) as a predictor of weaning outcome of patients with mechanical ventilation. Methods: An observational cohort study included 60 critically ill patients who were eligible for extubation. Pendelluft and electrical activity of the diaphragm (Edi) were monitored at baseline and every 10 minutes for the first 30 min of SBT denoted as T0, T1, T2, and T3. The pendelluft was measured using electrical impedance tomography (EIT), and Edi parameters were collected by Edi catheter. Patients were followed up after extubation and were divided into success group and failure group. Pendelluft, Edi parameters, respiratory parameters, and clinical outcomes such as intensive care units (ICU) stay, mortality, and 28-day ventilator-free days were compared between the two groups. Receiver operating characteristic (ROC) curves were constructed to evaluate the ability of pendelluft to predict weaning outcome. Results: Fifty patients (50/60) were successfully weaned from the machine and 10 (10/60) failed, with weaning failure rate of 16.7%. Respiratory parameters such as rapid shallow breathing index (RSBI), respiratory rate (RR) and Edi parameters such as maximum value of Edi (Edimax), Edi variation between a maximum and minimum(ΔEdi) in the failure group were higher than those in the success group. The ICU stay and the 28-day ventilator-free days in the failure group were significantly longer than those in the success group. The 28-day mortality rate was higher in the failure group. The pendelluft mainly occurred in the early stage of SBT. Ventral pendelluft and total pendelluft in the failure group were higher than those in the success group at T1. Edimax and ΔEdi were positively correlated with pendelluft. The area under ROC curve (AUC) showed moderate predictive ability for ventral pendelluft in predicting weaning failure at T1 (AUC 0.76, 95% CI 0.58-0.94, cut-off value > 3% global tidal variation). Conclusion: Pendelluft is one of the factors leading to weaning failure, which may be related to diaphragm function. Measuring pendelluft volume maybe helpful to predict weaning.
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PURPOSE: Our objective was to assess the incidence and dose-volume predictors of radiation esophagitis (RE) in patients with breast cancer undergoing hypofractionated regional nodal irradiation. METHODS AND MATERIALS: Eligible patients who received intensity modulated radiation therapy (RT) at the chest wall, the supraclavicular/infraclavicular fossa, level II axilla, and/or the internal mammary chain after mastectomy were included. The prescribed dose was 43.5 Gy in 15 fractions. RE was evaluated weekly during RT and at 1 and 2 weeks, followed by 3 and 6 months after RT, and was graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0. The esophagus was contoured from the lower border level of the cricoid cartilage to the lower margin of the aortic arch. Esophageal total volume, mean dose, maximum dose, and the relative volumes (RV) and absolute volumes (AV) receiving at least 5 to 45 Gy by 5-Gy increments (RV5-RV45 and AV5-AV45) were evaluated. Univariable and multivariable logistic regression analyses were performed to determine risk factors for RE, and receiver operating characteristic curves were obtained to identify the thresholds of esophageal dosimetric parameters. RESULTS: In total, 298 patients were included between May 8, 2020, and January 5, 2022 (minimum post-RT follow-up: 6 months). Grade 2 and 3 RE incidence was 40.9% (122/298) and 0.3% (1/298), respectively. No grade 4 or 5 RE was observed. Esophageal RV20-RV40 and AV35-AV40 were significantly associated with the risk of grade ≥2 RE after adjusting for tumor laterality and internal mammary nodal irradiation. RV25 and AV35 were optimum dose-volume predictors for grade ≥2 RE at thresholds 20% for RV25 (35.9% vs 60.9%; P = .04) and 0.27 mL for AV35 (31.0% vs 54.6%; P = .04). CONCLUSIONS: RE is common in patients with breast cancer undergoing hypofractionated regional nodal irradiation. Maintaining the upper esophageal V25 at <20% and V35 at <0.27 mL may decrease the risk of RE.
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Neoplasias da Mama , Esofagite , Parede Torácica , Humanos , Feminino , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia , Esofagite/epidemiologia , Esofagite/etiologia , MamaRESUMO
The emergence of the acute respiratory syndrome coronavirus 2 variant named Omicron has become a global concern. A 74-year-old unvaccinated patient was critically ill infected with the Omicron variant characterised by septic shock, large-scale cerebral embolism, deep vein thrombosis, and multiple organ dysfunction with respiratory failure, acute renal failure, coagulation dysfunction. The clinical symptoms were successfully controlled by active rescue treatment such as anti-infection, anti-shock, implantation of a vena cava filter as well as multi-organ function support. Although there are many complications in critically ill patients with Omicron variant infections, especially coagulation disorders and thrombosis, they can be resolved with a combination of Chinese and Western medicine positive rescue.
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COVID-19 , Choque Séptico , Trombose , Humanos , Idoso , Choque Séptico/diagnóstico , Choque Séptico/terapia , SARS-CoV-2 , Estado Terminal/terapia , COVID-19/complicações , Trombose/complicaçõesRESUMO
Lung injury is one of the leading causes of death in sepsis. Abietic acid (AA) has demonstrated anti-inflammatory and bacteriostatic properties. Herein, we established a mouse model of sepsis by cecal ligation and puncture, and intraperitoneally injected AA to treat. Lung injury was assessed by H&E staining and the inflammation in bronchoalveolar lavage fluid (BALF) were assessed by counting the number of inflammatory cells and detecting the content of inflammatory factors. Meanwhile, we also designed to study the effect of AA on lipopolysaccharide (LPS)-induced inflammatory response and macrophage marker gene expression in RAW264.7 cells in vitro. In this study, we found that AA inhibited LPS-induced secretion of inflammatory mediators (IL-1ß, TNF-α, IL-6 and MIP-2), and decreased the expression of M1 macrophage e markers (CD16 and iNOS) and p-p65 protein, while increased the expression of M2 macrophage markers (CD206 and Arg-1) in RAW264.7 cells in vitro. In vivo, the therapy of AA not only rescued septic animals, but also attenuated lung injury in sepsis mice. Moreover, AA decreased the number of total cells, neutrophils and macrophages, the conceration of total protein, and the levels of inflammatory mediators in BALF of sepsis mice. Further, we found that AA inhibited M1 macrophage polarization and blocked nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in BALF of sepsis mice. In conclusion, Abietic acid attenuates sepsis-induced lung injury, and its mechanism may be related to reducing inflammation by inhibiting NF-κB signaling to inhibit M1 macrophage polarization.
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Lesão Pulmonar Aguda , Sepse , Camundongos , Animais , NF-kappa B/metabolismo , Lipopolissacarídeos/efeitos adversos , Macrófagos/metabolismo , Sepse/complicações , Sepse/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/induzido quimicamente , Mediadores da Inflamação/metabolismo , InflamaçãoRESUMO
Background: The present study aimed to evaluate the frequency of silent cerebral small-vessel disease, especially lacunes and white matter hyperintensities, in patients with or without the impaired glucose tolerance (IGT) and type-2 diabetes mellitus, and to characterize the diabetes-correlated factors related to silent cerebral small-vessel disease. Methods: This is a retrospective cross-sectional study. Totally 698 patients were included in this study, from January 2014 to December 2019, among which 270 patients were included in the diabetes mellitus group, 106 patients were included in the IGT group, and 322 patients were included in the Control group. All patients underwent magnetic resonance imaging to investigate the silent cerebral small-vessel disease: the lacunes and the white matter hyperintensities. All the baseline information and diabetes-related factors, such as glycated hemoglobin level, insulin usage, etc., were collected. Then correlation analysis and regression analysis were used to explore the correlation between diabetes with related risk factors and silent cerebral small-vessel disease. Results: Lacunes and white matter hyperintensities were more common in the diabetes mellitus group than in the IGT group and the Control group, with an occurrence of lacunes of 83.3% vs. 70.8% vs. 70.4% (P=0.003), respectively, and an occurrence of white matter hyperintensities of 41.1% vs. 24.5% vs. 31.1% (P=0.003), respectively. The occurrence of lacunes was correlated with the duration of diabetes mellitus [odds ratio (OR) =1.483, 95% confidence interval (CI): 1.082-2.031, P=0.009] and the age (OR =1.141, 95% CI: 1.102-1.180, P<0.001), while white matter hyperintensities were independently correlated only with the age (OR =1.124, 95% CI: 1.094-1.155, P<0.001). Conclusions: Lacunes and white matter hyperintensities, are more common in the diabetes mellitus patients than in the IGT patients or in the other patients. The occurrence of lacunes was correlated with the duration of diabetes mellitus and the age, while the occurrence of white matter hyperintensities was independently correlated with the age.
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INTRODUCTION: Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a rare and life-threatening autoimmune disease. Immunoadsorption (IA) is a potential approach in treating AAV. PATIENTS AND METHODS: A 76-year-old male patient was admitted with hemoptysis and oliguria, progressed rapidly into pulmonary hemorrhaging, acute kidney damage, and multi-organ failure. He was diagnosed as MPO-ANCA-positive vasculitis by immunological detection and kidney biopsy in the case report. IA combined with methylprednisolone to induce and alleviate the disease effectively, and cyclophosphamide (0.2g every other day, a total of 1g for the first time, after the patients tolerated, 10mg/kg every 3 weeks for 6 months in total) combined with prednisone for maintenance therapy. RESULTS AND DISCUSSION: Although both kidneys suffered severe deterioration requiring long-term hemodialysis replacement therapy, their pulmonary function was restored. Furthermore, clinical and serological symptoms of the disease were successfully controlled. Consequently, IA treatment may quickly remove IgG and ANCA to efficiently control clinical symptoms, especially in patients presenting with alveolar hemorrhaging and acute renal failure.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Metilprednisolona , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Anticorpos Anticitoplasma de Neutrófilos , Citoplasma , Hemorragia/induzido quimicamente , Hemorragia/terapia , Humanos , Recém-Nascido , Masculino , Metilprednisolona/uso terapêuticoRESUMO
Post-radiation soft tissue sarcomas (PRSTSs) are rare secondary malignancies. In this report, we describe the clinical presentation of a 52-year-old woman who underwent postmastectomy radiation therapy (PMRT) for left-sided breast cancer 2.7 years ago and presented with a left internal mammary mass and left interpectoral nodule on computed tomography. On further evaluation, she was diagnosed with internal mammary rhabdomyosarcoma and interpectoral nodal breast cancer relapse, and was treated with chemotherapy, followed by surgery and endocrine therapy. She developed left pleural metastases and is currently receiving targeted therapy. Internal mammary rhabdomyosarcomas are rare among PRSTSs and pose a diagnostic challenge for patients with breast cancer. Histological evaluation is important for the differential diagnosis of breast cancer relapses with secondary malignancies. The management of post-radiation thoracic rhabdomyosarcomas is challenging, and the prognosis is poor.
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INTRODUCTION: Acute kidney injury (AKI) has high morbidity and mortality in intensive care units, which can lead to chronic kidney disease, more costs and longer hospital stay. Early identification of AKI is crucial for clinical intervention. Although various risk prediction models have been developed to identify AKI, the overall predictive performance varies widely across studies. Owing to the different disease scenarios and the small number of externally validated cohorts in different prediction models, the stability and applicability of these models for AKI in critically ill patients are controversial. Moreover, there are no current risk-classification tools that are standardised for prediction of AKI in critically ill patients. The purpose of this systematic review is to map and assess prediction models for AKI in critically ill patients based on a comprehensive literature review. METHODS AND ANALYSIS: A systematic review with meta-analysis is designed and will be conducted according to the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS). Three databases including PubMed, Cochrane Library and EMBASE from inception through October 2020 will be searched to identify all studies describing development and/or external validation of original multivariable models for predicting AKI in critically ill patients. Random-effects meta-analyses for external validation studies will be performed to estimate the performance of each model. The restricted maximum likelihood estimation and the Hartung-Knapp-Sidik-Jonkman method under a random-effects model will be applied to estimate the summary C statistic and 95% CI. 95% prediction interval integrating the heterogeneity will also be calculated to pool C-statistics to predict a possible range of C-statistics of future validation studies. Two investigators will extract data independently using the CHARMS checklist. Study quality or risk of bias will be assessed using the Prediction Model Risk of Bias Assessment Tool. ETHICS AND DISSEMINATION: Ethical approval and patient informed consent are not required because all information will be abstracted from published literatures. We plan to share our results with clinicians and publish them in a general or critical care medicine peer-reviewed journal. We also plan to present our results at critical care international conferences. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/X25AT.
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Injúria Renal Aguda , Estado Terminal , Injúria Renal Aguda/diagnóstico , Cuidados Críticos , Humanos , Unidades de Terapia Intensiva , Metanálise como Assunto , Revisões Sistemáticas como AssuntoRESUMO
White matter (WM) disease is recognized as an important cause of cognitive decline and dementia. White matter lesions (WMLs) appear as white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging (MRI) scans of the brain. Previous studies have shown that type 2 diabetes (T2DM) is associated with WMH. In this review, we reviewed the literature on the relationship between T2DM and WMH in PubMed and Cochrane over the past five years and explored the possible links among the presence of T2DM, the course or complications of diabetes, and WMH. We found that: (1) Both from a macro- and micro-scopic point of view, most studies support the relationship of a larger WMH and a decrease in the integrity of WMH in T2DM; (2) From the relationship between brain structural changes and cognition in T2DM, the poor performance in memory, attention, and executive function tests associated with abnormal brain structure is consistent; (3) Diabetic microangiopathy or peripheral neuropathy may be associated with WMH, suggesting that the brain may be a target organ for T2DM microangiopathy; (4) Laboratory markers such as insulin resistance and fasting insulin levels were significantly associated with WMH. High HbA1c and high glucose variability were associated with WMH but not glycemic control.
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Disfunção Cognitiva/etiologia , Diabetes Mellitus Tipo 2/complicações , Transtornos da Memória/etiologia , Substância Branca/fisiologia , Animais , Disfunção Cognitiva/patologia , Humanos , Transtornos da Memória/patologiaRESUMO
RATIONALE: Because of the lack of an antidote or effective treatment, patients with severe acute diquat and glyphosate poisoning always died within a few hours. Extracorporeal membrane pulmonary oxygenation (ECMO), as an artificial heart-lung supporting system, can be applied to support lung that is expected to recover from reversible pathological damage. However, to our knowledge, the application of ECMO for patients with diquat and glyphosate poisoning has not been reported. PATIENT CONCERNS: A 40-year-old man ingested in 100âml of diquat (20âg/100âml) and 400âml glyphosate (41âg/100âml) was admitted to the intensive care unit (ICU), immediately complicated by the development of ventricular fibrillation, respiratory failure, renal failure, and multi-organ failure. DIAGNOSIS: Diquat and glyphosate poisoning were diagnosed by stated ingestion history, and the diagnostic criteria for acute respiratory distress syndrome (ARDS) and multi-organ dysfunction syndrome were also met. INTERVENTIONS: He was treated with veno-venous ECMO. OUTCOMES: He was successfully transferred out of the ICU on day 46 and discharged on day 67. The computed tomography scan showed no obvious pulmonary fibrosis 2 months after poisoning. LESSONS: ECMO may be effective in the treatment of patients with severe ARDS caused by diquat and glyphosate poisoning when conventional management does not work.
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Diquat/intoxicação , Oxigenação por Membrana Extracorpórea/métodos , Glicina/análogos & derivados , Insuficiência de Múltiplos Órgãos/terapia , Síndrome do Desconforto Respiratório/terapia , Adulto , Glicina/intoxicação , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Síndrome do Desconforto Respiratório/induzido quimicamente , Resultado do Tratamento , GlifosatoRESUMO
OBJECTIVE: To identify genes regulated by HBV preS1-transactivated protein 2 binding protein 1 (PS1TP2BP1). METHODS: PS1TP2BP1 gene was amplified by polymerase chain reaction (PCR) technique and cloned into the eukaryotic expression vector pcDNA 3.1/my-c-His A. The mRNAs isolated from HepG2 cells transfected recombinant eukaryotic expression vector pcDNA 3.1/myc-HisA-PS1TP2BP1 and pcDNA 3.1/myc-HisA empty vector were used to construct subtractive library. The differentially expressed genes were identified and analyzed. RESULTS: 35 differentially expressed clones were obtained. Colony PCR identified 15 clones with 200-1000 bp inserts. Sequence analysis identified 15 differentially expressed genes. CONCLUSION: This study provides data for further characterize the function of PS1TP2BP1.
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Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B , Precursores de Proteínas/genética , Transativadores/genética , Sequência de Aminoácidos , Sequência de Bases , Proteínas de Transporte , Clonagem Molecular , Biblioteca Gênica , Vetores Genéticos , Células Hep G2 , Humanos , Dados de Sequência MolecularRESUMO
OBJECTIVE: To screen proteins in leukocytes interacting with PS1TP2 by yeast-two hybrid and to view their subcellular localization in HepG2 cells. METHODS: The function and structure of PS1TP2 were studied by bioinformatic analysis. PS1TP2 gene was amplified and cloned into plasmid pET32a (+) and pGBKT7 to construct recombinant expression vectors pET32a (+)-PS1TP2 and pGBKT7-PS1TP2. They were transduced into E. coli Rosetta strain and yeast AH109. The transformed yeast mated with yeast Y187 containing leukocyte cDNA library plasmid in a 2xYPDA medium. Diploid yeast cells were plated on a synthetic dropout nutrient medium (SD/-Trp-Leu-His-Ade) for selecting twice and then screening. Then a green fluorescent protein (GFP) expression vector pEGFP-C1-PS1TP2 was established, transduced into HepG2, and its subcellular localization was studied by fluorescence microscopy and confocal microscopy. RESULTS: Bioinformatic analysis showed that the PS1TP2 gene was located at 6q24.1, the protein was unstable and the aliphatic index was very high. After transformation of the E. coli and yeast AH109, the expression protein showed: (1) the molecular weight of the expressed product was about 41000 Da, and (2) PS1TP2 existed within the cells. Diploid yeast cells were plated on the synthetic dropout nutrient medium containing X-a-gal for selecting twice and then screening. Twenty-six colonies from blue colonies were sequenced, pEGFP-C1-PS1TP2 was successfully expressed in the HepG2 cells, and PS1TP2 was located in the cell plasma. CONCLUSION: A prokaryotic expression vector pET32a(+)-PS1TP2 was constructed successfully and the PS1TP2 was successfully expressed in the yeast system. Genes of PS1TP2 interact with leukocyte proteins. These results bring some new clues for studying the biological functions of HBV.
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Proteínas/genética , Proteínas/metabolismo , Sequência de Bases , Clonagem Molecular , Dipeptídeos , Expressão Gênica , Células Hep G2 , Antígenos de Superfície da Hepatite B/metabolismo , Humanos , Precursores de Proteínas/metabolismo , Técnicas do Sistema de Duplo-HíbridoRESUMO
AIM: To clone and identify human genes transactivated by PS1TP5 by constructing a cDNA subtractive library with suppression subtractive hybridization (SSH) technique. METHODS: SSH and bioinformatics techniques were used for screening and cloning of the target genes transactivated by PS1TP5 protein. The mRNA was isolated from HepG2 cells transfected with pcDNA3.1(-)-myc-his(A)-PS1TP5 and pcDNA3.1(-)-myc-his(A) empty vector, respectively, and SSH technique was employed to analyze the differentially expressed DNA sequence between the two groups. After digestion with restriction enzyme Rsa I, small size cDNAs were obtained. Then tester cDNA was divided into two groups and ligated to the specific adaptor 1 and adaptor 2, respectively. The tester cDNA was hybridized with driver cDNA twice and subjected to nested PCR for two times, and then subcloned into T/A plasmid vectors to set up the subtractive library. Amplification of the library was carried out with E. coli strain DH5alpha. The cDNA was sequenced and analyzed in GenBank with Vector NTI 9.1 and NCBI BLAST software after PCR amplification. RESULTS: The subtractive library of genes transactivated by PS1TP5 was constructed successfully. The amplified library contained 90 positive clones. Colony PCR showed that 70 clones contained 200-1000-bp inserts. Sequence analysis was performed in 30 clones randomly, and the full-length sequences were obtained by bioinformatics technique. Altogether 24 coding sequences were obtained, which consisted of 23 known and 1 unknown. One novel gene with unknown functions was found and named as PS1TP5TP1 after being electronically spliced, and deposited in GenBank (accession number: DQ487761). CONCLUSION: PS1TP5 is closely correlated with immunoregulation, carbohydrate metabolism, signal transduction, formation mechanism of hepatic fibrosis, and occurrence and development of tumor. Understanding PS1TP5 transactive proteins may help to bring some new clues for further studying the biological functions of pre-S1 protein.