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OBJECTIVE: Our study aimed to investigate the effects of different extracorporeal membrane oxygenation (ECMO) blood flow rates on lung perfusion assessment using the saline bolus-based electrical impedance tomography (EIT) technique in patients on veno-venous (VV) ECMO. METHODS: In this single-centered prospective physiological study, patients on VV ECMO who met the ECMO weaning criteria were assessed for lung perfusion using saline bolus-based EIT at various ECMO blood flow rates (gradually decreased from 4.5 L/min to 3.5 L/min, 2.5 L/min, 1.5 L/min, and finally to 0 L/min). Lung perfusion distribution, dead space, shunt, ventilation/perfusion matching, and recirculation fraction at different flow rates were compared. RESULTS: Fifteen patients were included. As the ECMO blood flow rate decreased from 4.5 L/min to 0 L/min, the recirculation fraction decreased significantly. The main EIT-based findings were as follows. (1) Median lung perfusion significantly increased in region-of-interest (ROI) 2 and the ventral region [38.21 (34.93-42.16)% to 41.29 (35.32-43.75)%, p = 0.003, and 48.86 (45.53-58.96)% to 54.12 (45.07-61.16)%, p = 0.037, respectively], whereas it significantly decreased in ROI 4 and the dorsal region [7.87 (5.42-9.78)% to 6.08 (5.27-9.34)%, p = 0.049, and 51.14 (41.04-54.47)% to 45.88 (38.84-54.93)%, p = 0.037, respectively]. (2) Dead space significantly decreased, and ventilation/perfusion matching significantly increased in both the ventral and global regions. (3) No significant variations were observed in regional and global shunt. CONCLUSIONS: During VV ECMO, the ECMO blood flow rate, closely linked to recirculation fraction, could affect the accuracy of lung perfusion assessment using hypertonic saline bolus-based EIT.
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Impedância Elétrica , Oxigenação por Membrana Extracorpórea , Pulmão , Tomografia , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Masculino , Feminino , Estudos Prospectivos , Impedância Elétrica/uso terapêutico , Pessoa de Meia-Idade , Adulto , Tomografia/métodos , Pulmão/irrigação sanguínea , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem , Solução Salina Hipertônica/uso terapêutico , Idoso , Velocidade do Fluxo Sanguíneo/fisiologiaRESUMO
Accumulated evidence suggested that gut microbial dysbiosis interplayed with progressive chronic kidney disease (CKD). However, no available therapy is effective in suppressing progressive CKD. Here, using microbiomics in 480 participants including healthy controls and patients with stage 1-5 CKD, we identified an elongation taxonomic chain Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus-Lactobacillus johnsonii correlated with patients with CKD progression, whose abundance strongly correlated with clinical kidney markers. L. johnsonii abundance reduced with progressive CKD in rats with adenine-induced CKD. L. johnsonii supplementation ameliorated kidney lesion. Serum indole-3-aldehyde (IAld), whose level strongly negatively correlated with creatinine level in CKD rats, decreased in serum of rats induced using unilateral ureteral obstruction (UUO) and 5/6 nephrectomy (NX) as well as late CKD patients. Treatment with IAld dampened kidney lesion through suppressing aryl hydrocarbon receptor (AHR) signal in rats with CKD or UUO, and in cultured 1-hydroxypyrene-induced HK-2 cells. Renoprotective effect of IAld was partially diminished in AHR deficiency mice and HK-2 cells. Our further data showed that treatment with L. johnsonii attenuated kidney lesion by suppressing AHR signal via increasing serum IAld level. Taken together, targeting L. johnsonii might reverse patients with CKD. This study provides a deeper understanding of how microbial-produced tryptophan metabolism affects host disease and discovers potential pathways for prophylactic and therapeutic treatments for CKD patients.
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Lactobacillus johnsonii , Insuficiência Renal Crônica , Insuficiência Renal Crônica/microbiologia , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/patologia , Animais , Ratos , Humanos , Camundongos , Masculino , Lactobacillus johnsonii/genética , Indóis , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Microbioma Gastrointestinal , FemininoRESUMO
Sepsis is a critical global health concern linked to high mortality rates, often due to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). While the gut-lung axis involvement in ALI is recognized, direct migration of gut immune cells to the lung remains unclear. Our study reveals sepsis-induced migration of γδ T17 cells from the small intestine to the lung, triggering an IL-17A-dominated inflammatory response in mice. Wnt signaling activation in alveolar macrophages drives CCL1 upregulation, facilitating γδ T17 cell migration. CD44+ Ly6C- IL-7Rhigh CD8low cells are the primary migratory subtype exacerbating ALI. Esketamine attenuates ALI by inhibiting pulmonary Wnt/ß-catenin signaling-mediated migration. This work underscores the pivotal role of direct gut-to-lung memory γδ T17 cell migration in septic ALI and clarifies the importance of localized IL-17A elevation in the lung.
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Lesão Pulmonar Aguda , Movimento Celular , Interleucina-17 , Pulmão , Camundongos Endogâmicos C57BL , Sepse , Animais , Sepse/imunologia , Sepse/complicações , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Camundongos , Interleucina-17/metabolismo , Interleucina-17/imunologia , Pulmão/imunologia , Pulmão/patologia , Masculino , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Via de Sinalização Wnt/imunologia , Macrófagos Alveolares/imunologia , Intestino Delgado/imunologia , Intestino Delgado/patologia , Linfócitos Intraepiteliais/imunologia , Modelos Animais de Doenças , Antígenos Ly/metabolismo , Memória ImunológicaRESUMO
Sepsis-associated encephalopathy (SAE) is a collection of clinical syndromes resulting from sepsis and characterized by widespread brain dysfunction. The high prevalence of SAE has adverse outcomes on the clinical management and prognosis of sepsis patients. However, currently, there are no effective treatments to ameliorate SAE. The pathogenesis of SAE is complex, including neuroinflammation and microglia activation, destruction of the blood-brain barrier (BBB), neurotransmitter dysfunction, cerebral metabolism and mitochondrial impairment, accumulation of amyloid beta and tauopathy, complement activation, among others. Furthermore, these mechanisms intertwine with each other, further complicating the comprehension of SAE. Among them, neuroinflammation mediated by hyperactivated microglia is considered the primary etiology of SAE. This instigates a detrimental cycle wherein BBB permeability escalates, facilitating direct damage to the central nervous system (CNS) by various neurotoxic substances. Activation of the NLRP3 inflammasome, situated within microglia, can be triggered by diverse danger signals, leading to cell pyroptosis, apoptosis, and tauopathy. These complex processes intricately regulate the onset and progression of neuroinflammation. In this review, we focus on elucidating the inhibitory regulatory mechanism of the NLRP3 inflammasome in microglia, which ultimately manifests as suppression of the inflammatory response. Our ultimate objective is to augment comprehension regarding the role of microglial NLRP3 inflammasome as we explore potential targets for therapeutic interventions against SAE.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Encefalopatia Associada a Sepse , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Encefalopatia Associada a Sepse/metabolismo , Encefalopatia Associada a Sepse/tratamento farmacológico , Inflamassomos/metabolismo , Animais , Microglia/metabolismo , Microglia/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismoRESUMO
Enterovirus 71 (EV71), a prominent pathogen associated with hand, foot, and mouth disease (HFMD), has been reported worldwide. To date, the advancement of effective drugs targeting EV71 remains in the preliminary experimental stage. In this study, magnolol demonstrated a significant dose-dependent inhibition of EV71 replication in vitro. It upregulated the overall expression level of nuclear factor erythroid 2 - related factor 2 (Nrf2) and facilitated its nucleus translocation, resulting in the increased expression of various ferroptosis inhibitory genes. This process led to a reduction in reactive oxygen species (ROS) accumulation induced by viral infection. Additionally, magnolol exhibited a broad-spectrum antiviral effect against enteroviruses. Notably, treatment with magnolol substantially enhanced the survival rate of EV71-infected mice, attenuated viral load in heart, liver, brain, and limb tissues, and mitigated tissue inflammation. Taken together, magnolol emerges as a promising candidate for the development of anti-EV71 drugs.
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Antivirais , Compostos de Bifenilo , Enterovirus Humano A , Lignanas , Fator 2 Relacionado a NF-E2 , Animais , Compostos de Bifenilo/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Lignanas/farmacologia , Enterovirus Humano A/efeitos dos fármacos , Antivirais/farmacologia , Camundongos , Humanos , Glutationa/metabolismo , Replicação Viral/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Infecções por Enterovirus/tratamento farmacológico , Infecções por Enterovirus/virologia , Transdução de Sinais/efeitos dos fármacos , Chlorocebus aethiops , Células Vero , Ferroptose/efeitos dos fármacosAssuntos
Relação Dose-Resposta a Droga , Hipnóticos e Sedativos , Unidades de Terapia Intensiva , Propofol , Humanos , Propofol/administração & dosagem , Propofol/efeitos adversos , Propofol/análogos & derivados , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Adulto , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Sedação Consciente/métodos , Sedação Consciente/efeitos adversosRESUMO
OBJECTIVES: This study aimed to investigate the role of BMP2 in hepatocellular carcinoma (HCC) growth and metastasis using a dual approach combining single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq. METHODS: scRNA-seq data from the GEO database and bulk RNA-seq data from the TCGA database were analyzed. Differentially expressed marker genes of endothelial cells were identified and analyzed using enrichment analysis, PPI analysis, correlation analysis, and GSEA. In vitro, experiments were conducted using the Huh-7 HCC cell line, and in vivo, models of HCC growth and metastasis were established by knocking down BMP2. RESULTS: The scRNA-seq analysis identified BMP2 as a key marker gene in endothelial cells of HCC samples. Elevated BMP2 expression correlated with poor prognosis in HCC. In vitro experiments showed that silencing BMP2 inhibited the proliferation, migration, and invasion of liver cancer cells. In vivo studies confirmed increased BMP2 expression in HCC tissues, promoting angiogenesis and HCC growth. CONCLUSION: This study highlights the role of BMP2 in tumor angiogenesis and HCC progression. Targeting BMP2 could be a promising therapeutic strategy against HCC.
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Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in patients with severe fever with thrombocytopenia syndrome (SFTS), yet SFTS-associated IPA (SAPA)'s risk factors remain undefined. A multicenter retrospective cohort study across Hubei and Anhui provinces (May 2013-September 2022) utilized least absolute shrinkage and selection operator (LASSO) regression for variable selection. Multivariable logistic regression identified independent predictors of SAPA, Cox regression highlighted mortality-related risk factors. Of the 1775 screened SFTS patients, 1650 were included, with 169 developing IPA, leading to a 42-day mortality rate of 26.6% among SAPA patients. Multivariable logistic regression revealed SAPA risk factors including advanced age, petechia, hemoptysis, tremor, low albumin levels, elongated activated partial thromboplastin time (APTT), intensive care unit (ICU) admission, glucocorticoid usage, intravenous immunoglobulin (IVIG) and prolonged hospital stays. Cox regression identified predictors of 42-day mortality, including ecchymosis at venipuncture sites, absence of ICU admission, elongated prothrombin time (PT), vasopressor and glucocorticoid use, non-antifungals. Nomograms constructed on these predictors registered concordance indexes of 0.855 (95% CI: 0.826-0.884) and 0.778 (95% CI: 0.702-0.854) for SAPA onset and 42-day mortality, respectively. Lower survival rates for SAPA patients treated with glucocorticoids (p < 0.001) and improved 14-day survival with antifungal therapy (p = 0.036). Improving IPA management in SFTS-endemic areas is crucial, with effective predictive tool.
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Aspergilose Pulmonar Invasiva , Febre Grave com Síndrome de Trombocitopenia , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Aspergilose Pulmonar Invasiva/mortalidade , Aspergilose Pulmonar Invasiva/complicações , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Febre Grave com Síndrome de Trombocitopenia/complicações , Idoso , China/epidemiologia , AdultoRESUMO
Osteoarthritis (OA) is a common degenerative joint disease, and subchondral osteosclerosis is an important pathological change that occurs in its late stages. Cardamonin (CD) is a natural flavonoid isolated from Alpinia katsumadai that has anti-inflammatory activity. The objectives of this study were to investigate the therapeutic effects and potential mechanism of CD in regulating OA subchondral osteosclerosis at in vivo and in vitro settings. Eight-week-old male C57BL/6J mice were randomly divided into four groups: sham operation, anterior cruciate ligament transection (ACLT)-induced OA model, low-dose and high-dose CD treated ACLT-OA model groups. Histological assessment and immunohistochemical examinations for chondrocyte metabolism-related markers metalloproteinase-13, ADAMTS-4, Col II, and Sox-9 were performed. Microcomputed tomography was used to assess the sclerosis indicators in subchondral bone. Further, MC3T3-E1 (a mouse calvarial preosteoblast cell line) cells were treated with various concentrations of CD to reveal the influence and potential molecular pathways of CD in osteogenic differentiations. Animal studies suggested that CD alleviated the pathological changes in OA mice such as maintaining integrity and increasing the thickness of hyaline cartilage, decreasing the thickness of calcified cartilage, decreasing the Osteoarthritis Research Society International score, regulating articular cartilage metabolism, and inhibiting subchondral osteosclerosis. In vitro investigation indicated that CD inhibited alkaline phosphatase expression and production of calcium nodules during osteogenic differentiation of MC3T3-E1 cells. In addition, CD inhibited the expression of osteogenic differentiation-related indicators and Wnt/ß-catenin pathway-related proteins. In conclusion, CD inhibits osteogenic differentiation by downregulating Wnt/ß-catenin signaling and alleviating subchondral osteosclerosis in a mouse model of OA.
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Diferenciação Celular , Chalconas , Camundongos Endogâmicos C57BL , Osteoartrite , Osteogênese , Osteosclerose , Via de Sinalização Wnt , Animais , Masculino , Chalconas/farmacologia , Chalconas/uso terapêutico , Osteogênese/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Camundongos , Osteosclerose/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Diferenciação Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , beta Catenina/metabolismoRESUMO
STUDY OBJECTIVE: Fospropofol disodium is a propofol prodrug that is water-soluble and has a reduced risk of bacterial contamination and hypertriglyceridemia compared with propofol. Prior to implementing a large randomized trial, we investigated the feasibility, initial efficacy, and safety of fospropofol disodium compared with propofol in long-term mild-to-moderate sedation in intensive care units (ICUs). DESIGN: Single-centered, prospective, unblind, randomized, parallel-group clinical trial. SETTING: The general ICU of university-affiliated teaching hospital. PATIENTS: Adult patients (n = 60) expected to have mechanical ventilation for >24 h were enrolled and randomly assigned to the fospropofol or propofol group. INTERVENTIONS: The fospropofol group received continuous fospropofol disodium infusions and the propofol group received continuous propofol infusions. The sedation goal was a score of -3 to 0 on the Richmond Agitation and Sedation Scale (RASS). MEASUREMENTS: The primary outcome was the percentage of time spent in the target sedation range without rescue sedation. Safety outcomes were based on adverse events. Blood samples were collected to measure formate concentration in plasma. MAIN RESULTS: The median dose was 4.33 (IQR, 3.08-4.94) mg/kg/h in the fospropofol group and 1.96 (IQR, 1.44-2.94) mg/kg/h in the propofol group. The median percentage of time spent in the target RASS range without rescue sedation was identical in both groups, with 83.33% (IQR, 74.43%-100.00%) in the fospropofol group and 83.33% (IQR, 77.45%-100.00%) in the propofol group (p = 0.887). At least one adverse event was identifed in 23 (76.7%) fospropofol patients and 27 (90.0%) propofol patients. The most common adverse events were tachycardia and hypotension. No paresthesia, catheter-related bloodstream infection or propofol infusion syndrome in both groups was reported. Three patients in the fospropofol group had mild hypertriglyceridemia, and nine patients in propofol group had hypertriglyceridemia (mild in eight patients and moderate in one patient) (10% versus 30%, p = 0.104). The formate concentration in plasma was very low, and no significant difference was identified at any time point between the two groups. CONCLUSIONS: Fospropofol disodium appears to be a feasible, effective and safe sedative for patients receiving invasive mechanical ventilation with long-term sedation.
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Hipnóticos e Sedativos , Propofol , Propofol/análogos & derivados , Respiração Artificial , Humanos , Propofol/administração & dosagem , Propofol/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Projetos Piloto , Respiração Artificial/efeitos adversos , Estudos Prospectivos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Idoso , Unidades de Terapia Intensiva , Estudos de Viabilidade , Adulto , Sedação Consciente/métodos , Sedação Consciente/efeitos adversos , Infusões Intravenosas , Pró-Fármacos/administração & dosagem , Pró-Fármacos/efeitos adversosRESUMO
Background: This study aimed to retrospectively investigate the early predictive value of inflammation-related parameters in-hospital mortality of septic patients. Methods: We retrospectively recruited 606 patients from Wuhan Union Hospital from January 2009 to October 2022. The inflammation-related parameters including neutrophil-to-lymphocyte ratio (NLR), neutrophil percentage (NE%), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in survivals and non-survivals on day 1, 2, 3 and 7 after hospitalization were collected and analyzed. Results: NLR and NE% in non-survivals (n = 185) were significantly higher than those in survivals (n = 421). The area under the receiver operating characteristic curve (AUC) of NLR or NE% was 0.880 or 0.852 on day 1, 0.770 or 0.790 on day 2, 0.784 or 0.777 on day 3, and 0.732 or 0.741 on day 7. The optimal cut-off values of NLR or NE% for predicting in-hospital mortality were 10.769 or 87.70% on day 1, 17.544 or 90.69% on day 2, 14.395 or 85.00% on day 3, and 9.105 or 83.93% on day 7. The day 1, 2 and 3 NLR and NE% were significant predictors of in-hospital mortality in the Cox proportional hazards models. Conclusions: NLR ≥10.769 and NE% ≥ 87.70% could be used early biomarkers for predicting in-hospital mortality of septic patients.
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The clinical research in the field of extracorporeal life support (ECLS) in 2023 has focused on the efficacy of veno-arterial extracorporeal membrane oxygenation (ECMO) in patients with infarct-related cardiogenic shock. Additionally, the research also explored the efficacy of prone positioning during veno-venous ECMO, transfusion strategies, and the impact of obesity on outcomes. Awake veno-venous ECMO has shown novel therapeutic potential, but its optimal practice methods and management strategies remain to be determined. In in-hospital cardiac arrest patients, extracorporeal cardiopulmonary resuscitation has demonstrated higher survival rates and better neurological recovery compared to conventional cardiopulmonary resuscitation. The effectiveness of extracorporeal carbon dioxide removal varies among patients with different types of respiratory failure. Future research should focus on optimizing the application strategies and process management of ECLS technologies, investigating personalized therapy, and studying how to improve long-term rehabilitation and quality of life for survivors.
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Reanimação Cardiopulmonar , Oxigenação por Membrana Extracorpórea , Humanos , Qualidade de Vida , Posicionamento do Paciente , Diálise RenalRESUMO
Sufentanil is a common opioid anesthetic agent, which exerts anti-cancer properties in several cancer types. However, its action mechanisms in non-small cell lung cancer (NSCLC) are unclear. Therefore, the present study investigated the pharmacological effect of sufentanil on miRNAs in NSCLC treatment. In this study, after treatment with sufentanil, the proliferation, migration, invasion and apoptosis of A549 and H1299 NSCLC cell lines were measured by cell counting kit-8 (CCK-8) assay, colony formation assay, transwell assays and flow cytometry. Quantitative real time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of miR-186-5p and high mobility group box-1 (HMGB1), and their interaction was analyzed using luciferase reporter assay. The proteins of HMGB1, and apoptosis- and Wnt/ß-catenin pathway-related factors were detected by western blot. It was demonstrated that sufentanil significantly upregulated miR1865p to restrict NSCLC cell proliferation, migration, invasion, and boost apoptosis in vitro. Mechanically, miR-186-5p interacted with HMGB1 and negatively regulated HMGB1 in NSCLC cells. Furthermore, rescue assay showed that sufentanil exerted antitumor activities by upregulating miR-186-5p, which targeted HMGB1 and restrained Wnt/ß-catenin signal pathway in NSCLC cells. In conclusion, these results suggested that sufentanil disrupts the oncogenicity of NSCLC cells by regulating miR-186-5p/HMGB1/ß-catenin axis, providing a promising implication for the anti-oncogenic effect of sufentanil.
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Sepsis, a common life-threatening clinical condition, continues to have high morbidity and mortality rates, despite advancements in management. In response, significant research efforts have been directed toward developing effective strategies. Within this scope, nanotechnology has emerged as a particularly promising field, attracting significant interest for its potential to enhance disease diagnosis and treatment. While several reviews have highlighted the use of nanoparticles in sepsis, comprehensive studies that summarize and analyze the hotspots and research trends are lacking. To identify and further promote the development of nanotechnology in sepsis, a bibliometric analysis was conducted on the relevant literature, assessing research trends and hotspots in the application of nanomaterials for sepsis. Next, a comprehensive review of the subjectively recognized research hotspots in sepsis, including nanotechnology-enhanced biosensors and nanoscale imaging for sepsis diagnostics, and nanoplatforms designed for antimicrobial, immunomodulatory, and detoxification strategies in sepsis therapy, is elucidated, while the potential side effects and toxicity risks of these nanomaterials were discussed. Particular attention is given to biomimetic nanoparticles, which mimic the biological functions of source cells like erythrocytes, immune cells, and platelets to evade immune responses and effectively deliver therapeutic agents, demonstrating substantial translational potential. Finally, current challenges and future perspectives of nanotechnology applications in sepsis with a view to maximizing their great potential in the research of translational medicine are also discussed.
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Nanopartículas , Nanoestruturas , Sepse , Humanos , Nanotecnologia/métodos , Nanoestruturas/uso terapêutico , Nanopartículas/uso terapêutico , Diagnóstico por Imagem , Sepse/diagnóstico , Sepse/terapiaRESUMO
INTRODUCTION: Previous studies suggested that electrical impedance tomography (EIT) has the potential to guide positive end-expiratory pressure (PEEP) titration via quantifying the alveolar collapse and overdistension. The aim of this trial is to compare the effect of EIT-guided PEEP and acute respiratory distress syndrome (ARDS) network low PEEP/fraction of inspired oxygen (FiO2) table strategy on mortality and other clinical outcomes in patients with ARDS. METHODS: This is a parallel, two-arm, multicentre, randomised, controlled trial, conducted in China. All patients with ARDS under mechanical ventilation admitted to the intensive care unit will be screened for eligibility. The enrolled patients are stratified by the aetiology (pulmonary/extrapulmonary) and partial pressure of arterial oxygen/FiO2 (≥150 mm Hg or <150 mm Hg) and randomised into the intervention group or the control group. The intervention group will receive recruitment manoeuvre and EIT-guided PEEP titration. The EIT-guided PEEP will be set for at least 12 hours after titration. The control group will not receive recruitment manoeuvre routinely and the PEEP will be set according to the lower PEEP/FiO2 table proposed by the ARDS Network. The primary outcome is 28-day survival. ANALYSIS: Qualitative data will be analysed using the χ2 test or Fisher's exact test, quantitative data will be analysed using independent samples t-test or Mann-Whitney U test. Kaplan-Meier analysis with log-rank test will be used to evaluate the 28-day survival rate between two groups. All outcomes will be analysed based on the intention-to-treat principle. ETHICS AND DISSEMINATION: The trial is approved by the Institutional Research and Ethics Committee of the Peking Union Medical College Hospital. Data will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05307913.
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Síndrome do Desconforto Respiratório , Humanos , Impedância Elétrica , Prognóstico , Síndrome do Desconforto Respiratório/terapia , Tomografia , Oxigênio , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Sepsis and septic shock remain the leading causes of death in intensive care units. Some patients with sepsis fail to respond to routine treatment and rapidly progress to refractory respiratory and circulatory failure, necessitating extracorporeal membrane oxygenation (ECMO). However, the role of ECMO in adult patients with sepsis has not been fully established. According to existing studies, ECMO may be a viable salvage therapy in carefully selected adult patients with sepsis. The choice of venovenous, venoarterial, or hybrid ECMO modes is primarily determined by the patient's oxygenation and hemodynamics (distributive shock with preserved cardiac output, septic cardiomyopathy (left, right, or biventricular heart failure), or right ventricular failure caused by acute respiratory distress syndrome). Veno-venous ECMO can be used in patients with sepsis and severe acute respiratory distress syndrome when conventional mechanical ventilation fails, and early application of veno-arterial ECMO in patients with sepsis-induced refractory cardiogenic shock may be critical in improving their chances of survival. When ECMO is indicated, the choice of an appropriate mode and determination of the optimal timing of initiation and weaning are critical, particularly in an experienced ECMO center. Furthermore, some special issues, such as ECMO flow, anticoagulation, and antibiotic therapy, should be noted during the management of ECMO support.
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OBJECTIVE: To compare the efficacy and safety of remimazolam besylate and propofol for deep sedation in critically ill patients. METHODS: In this single-center, prospective, randomized, controlled pilot study, patients in the intensive care unit (ICU) requiring deep sedation were randomized to receive remimazolam besylate or propofol intravenously. Deep sedation was defined as a Richmond Agitation and Sedation Scale (RASS) score of - 4 or - 5. Sedation depth was monitored using RASS and Narcotrend Index (NI). The primary outcome was the percentage of time within the target sedation range without rescue sedation. The secondary outcomes included ventilator-free hours within 7 days, successful extubation, length of ICU stay, and 28-day mortality. Adverse events during the interventional period were also recorded. RESULTS: Thirty patients were assigned to each group. The median (IQR) RASS score was - 5.0 (- 5.0, - 4.0), and the median (IQR) NI value was 29.0 (21.0, 37.0) during the intervention period. Target RASS was reached a median of 100% of the sedation time in the two groups. No significant differences were observed in ventilator-free hours within 7 days, successful extubation, length of ICU stay, or 28-day mortality among groups. Hypotension occurred in 16 (53.3%) patients of remimazolam group and 18 (60.0%) patients of propofol group (p > 0.05). No patient experienced bradycardia. CONCLUSIONS: Remimazolam besylate appears to be an effective and safe agent for short-term deep sedation in critically ill patients. Our findings warrant large sample-sized randomized clinical trials.
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Sedação Profunda , Propofol , Humanos , Estado Terminal/terapia , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Projetos Piloto , Propofol/farmacologia , Propofol/uso terapêutico , Estudos Prospectivos , Respiração ArtificialRESUMO
OBJECTIVE: The activation state of microglia is known to occupy a central position in the pathophysiological process of cerebral inflammation. Autophagy is a catabolic process responsible for maintaining cellular homeostasis. In recent years, autophagy has been demonstrated to play an important role in neuroinflammation. Resolvin D1 (RvD1) is a promising therapeutic mediator that has been shown to exert substantial anti-inflammatory and proresolving activities. However, whether RvD1-mediated resolution of inflammation in microglia is related to autophagy regulation needs further investigation. The present study aimed to explore the effect of RvD1 on microglial autophagy and its corresponding pathways. METHODS: Mouse microglial cells (BV-2) were cultured, treated with RvD1, and examined by Western blotting, confocal immunofluorescence microscopy, transmission electron microscopy, and flow cytometry. RESULTS: RvD1 promoted autophagy in both BV-2 cells and mouse primary microglia by favoring the maturation of autophagosomes and their fusion with lysosomes. Importantly, RvD1 had no significant effect on the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, RvD1-induced mTOR-independent autophagy was confirmed by observing reduced cytoplasmic calcium levels and suppressed calcium/calmodulin-dependent protein kinase II (CaMK II) activation. Moreover, by downregulating ATG5, the increased phagocytic activity induced by RvD1 was demonstrated to be tightly controlled by ATG5-dependent autophagy. CONCLUSION: The present work identified a previously unreported mechanism responsible for the role of RvD1 in microglial autophagy, highlighting its therapeutic potential against neuroinflammation.
Assuntos
Microglia , Doenças Neuroinflamatórias , Camundongos , Animais , Cálcio/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , MamíferosRESUMO
Chronic wounds have been a global health risk that demands intensive exploration. A tri-layered biomaterial scaffold has been developed for skin wounds. The top layer of the scaffold is superhydrophobic, and the bottom layer is hydrophilic, both of which were electrospun using recycled expanded polystyrene (EPS) and monofilament fishing line (MFL), respectively. The intermediate layer of the scaffold comprised hydrogel by cross-linking chitosan (CS) with polyethylene glycol. The surface morphology, surface chemistry, thermal degradation, and wettability characteristics of each layer of the scaffold were examined. Also, the antibacterial activity and in vitro cytotoxicity study on the combined tri-layered scaffold were assessed against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Data revealed exceptional water repellency of the heat-treated electrospun top superhydrophobic layer (TSL) with a high-water contact angle (WCA) of 172.44°. A TSL with 15 wt% of micro-/nano-inclusions had the best thermal stability above 400 °C. The bottom hydrophilic layer (BHL) displayed a WCA of 9.91°. Therapeutically, the synergistic effect of the combined tri-layered scaffold significantly inhibited bacteria growth by 70.5% for E. coli and 68.6% for S. aureus. Furthermore, cell viability is enhanced when PEG is included as part of the intermediate CS hydrogel layer (ICHL) composition.