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OBJECTIVE: To explore the influence of classroom-based physical activity (CB-PA) on the teaching quality of systemic lupus erythematosus (SLE) for medical undergraduates. METHODS: Students from 8 classes participating in the clinical medicine program of the affiliated hospital of Zunyi Medical University were divided into two groups. Four classes received regular teaching on the SLE chapter as the control group, and the other four received CB-PA intervention as the experimental group. After class, the basic ability (diagnostics and pharmacology scores in sophomore year) and teaching quality scores were collected and compared using a questionnaire. The performance of the 2 groups to the SLE review questions was compared. RESULTS: The scores of learning interest, the degree of satisfaction with the courses, and the level of mastering the teaching contents in the experimental group were significantly higher than those in the control group. The evaluation of the teacher's teaching level increased considerably. The experimental group's performance was also better than the control group's (the assessment performance was adjusted with the basic ability). CONCLUSION: CB-PA in teaching SLE improves students' interest in learning, teaching satisfaction, and mastery of knowledge and may ultimately enhance their assessment results.
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Lúpus Eritematoso Sistêmico , Humanos , Estudantes , Inquéritos e QuestionáriosRESUMO
Molecular oxygen is typically delivered to patients via oxygen inhalation or extracorporeal membrane oxygenation (ECMO), potentially resulting in systemic hyperoxia from liberal oxygen inhalation or localized hyperoxia in the lower body from peripheral venoarterial (VA) ECMO. Consequently, this exposes the gastrointestinal tract to excessive oxygen levels. Hyperoxia can trigger organ damage due to the overproduction of reactive oxygen species and is associated with increased mortality. The gut and gut microbiome play pivotal roles in critical illnesses and even small variations in oxygen levels can have a dramatic influence on the physiology and ecology of gut microbes. Here, we reviewed the emerging preclinical evidence which highlights how excessive inhaled oxygen can provoke diffuse villous damage, barrier dysfunction in the gut, and gut dysbiosis. The hallmark of this dysbiosis includes the expansion of oxygen-tolerant pathogens (e.g., Enterobacteriaceae) and the depletion of beneficial oxygen-intolerant microbes (e.g., Muribaculaceae). Furthermore, we discussed potential impact of oxygen on the gut in various underlying critical illnesses involving inspiratory oxygen and peripheral VA-ECMO. Currently, the available findings in this area are somewhat controversial, and a consensus has not yet to be reached. It appears that targeting near-physiological oxygenation levels may offer a means to avoid hyperoxia-induced gut injury and hypoxia-induced mesenteric ischemia. However, the optimal oxygenation target may vary depending on special clinical conditions, including acute hypoxia in adults and neonates, as well as particular patients undergoing gastrointestinal surgery or VA-ECMO support. Last, we outlined the current challenges and the need for future studies in this area. Insights into this vital ongoing research can assist clinicians in optimizing oxygenation for critically ill patients.
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Hiperóxia , Adulto , Recém-Nascido , Humanos , Hiperóxia/complicações , Estado Terminal/terapia , Disbiose , Oxigênio/efeitos adversos , HipóxiaRESUMO
BACKGROUND AND AIM: A strong association between family function and irritable bowel syndrome (IBS) has been observed. Parental rearing styles, as a comprehensive mark for family function, may provide new clues to the etiology of IBS. This study aimed to explore which dimensions of parental rearing styles were risk factors or protective factors for IBS in adolescents. METHODS: Two thousand three hundred twenty adolescents were recruited from one middle school and one high school randomly selected from Jiangan District (an urban district in Wuhan City). Data were collected using two Chinese versions of validated self-report questionnaires including the Rome III diagnostic criteria for pediatric IBS and the Egna Minnen Beträffande Uppfostran: One's Memories of Upbringing for perceived parental rearing styles. RESULTS: Ninety-six subjects diagnosed as pediatric IBS were compared with 1618 controls. The IBS patients reported less both paternal and maternal emotional warmth (all P < 0.01) and more both paternal and maternal punishment, overinterference, rejection, and overprotection (only for father) (all P < 0.01) than the controls. Furthermore, the IBS patients had higher total scores of parental rearing styles (all P < 0.001) than the controls. With univariate logistic regression, standardized regression coefficients and odds ratios of parental rearing variables were calculated. Multivariate logistic regression revealed that paternal rejection (P = 0.001) and maternal overinterference (P = 0.002) were independent risk factors for IBS in adolescents. CONCLUSIONS: Parental emotional warmth is a protective factor for IBS in adolescents and parental punishment, overinterference, rejection, and overprotection are risk factors for IBS in adolescents.
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Educação Infantil/psicologia , Síndrome do Intestino Irritável/etiologia , Síndrome do Intestino Irritável/psicologia , Relações Pais-Filho , Pais/psicologia , Adolescente , Criança , Emoções/fisiologia , Feminino , Humanos , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/prevenção & controle , Modelos Logísticos , Masculino , Punição/psicologia , Rejeição em Psicologia , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Chondrocyte ferroptosis plays a critical role in the pathogenesis of osteoarthritis (OA), regulated by the SLC7A11/GPX4 signaling pathway. Icariin (ICA), a flavonoid glycoside, exhibits strong anti-inflammatory and antioxidant activities. This study investigated whether ICA could modulate the SLC7A11/GPX4 signaling to inhibit chondrocyte ferroptosis and alleviate OA. PURPOSE: The objective was to explore the impact of ICA on chondrocyte ferroptosis in OA and its modulation of the SLC7A11/GPX4 signaling pathway. METHODS: The anti-ferroptosis effects of ICA were evaluated in an interleukin-1ß (IL-1ß)-treated SW1353 cell model, using Ferrostatin-1 (Fer-1) and Erastin (Era) as ferroptosis inhibitor and inducer, respectively, along with GPX4 knockdown via lentivirus-based shRNA. Additionally, the therapeutic efficacy of ICA on OA-related articular cartilage damage was assessed in rats through histopathology and immunohistochemistry (IHC). RESULTS: IL-1ß treatment upregulated the expression of OA-associated matrix metalloproteinases (MMP3 and MMP1), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-5), and increased intracellular ROS, lipid ROS, and MDA levels while downregulating collagen II and SOX9 expression in SW1353 cells. ICA treatment countered the IL-1ß-induced upregulation of MMPs and ADAMTS-5, restored collagen II and SOX9 expression, and reduced intracellular ROS, lipid ROS, and MDA levels. Furthermore, IL-1ß upregulated P53 but downregulated SLC7A11 and GPX4 expression in SW1353 cells, effects that were mitigated by ICA or Fer-1 treatment. Significantly, ICA also alleviated Era-induced ferroptosis, whereas it had no effect on GPX4-silenced SW1353 cells. In vivo, ICA treatment reduced articular cartilage damage in OA rats by partially restoring collagen II and GPX4 expression, inhibiting cartilage extracellular matrix (ECM) degradation and chondrocyte ferroptosis. CONCLUSION: ICA treatment mitigated chondrocyte ferroptosis and articular cartilage damage by enhancing the SLC7A11/GPX4 signaling, suggesting its potential as a therapeutic agent for OA interventions.
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Sistema y+ de Transporte de Aminoácidos , Condrócitos , Ferroptose , Flavonoides , Osteoartrite , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Transdução de Sinais , Animais , Humanos , Masculino , Ratos , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Cartilagem Articular/metabolismo , Linhagem Celular , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Ferroptose/efeitos dos fármacos , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Interleucina-1beta/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Osteoartrite/patologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To observe and verify the changes of transcriptome in hyperoxia-induced acute lung injury (HALI), and to further clarify the changes of pathways in HALI. METHODS: Twelve healthy male C57BL/6J mice were randomly divided into normoxia group and HALI group according to the random number table, with 6 mice in each group. The mice in the normoxia group were fed normally in the room, and the mice in the HALI group was exposed to 95% oxygen to reproduce the HALI animal model. After 72 hours of hyperoxia exposure, the lung tissues were taken for transcriptome sequencing, and then Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathway enrichment analysis was performed. The pathological changes of lung tissue were observed under light microscope after hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to verify the key molecules in the signal pathways closely related to HALI identified by transcriptomics analysis. RESULTS: Transcriptomic analysis showed that hyperoxia induced 537 differentially expressed genes in lung tissue of mice as compared with the normoxia group including 239 up-regulated genes and 298 down-regulated genes. Further KEGG pathway enrichment analysis identified 20 most significantly enriched pathway entries, and the top three pathways were ferroptosis signaling pathway, p53 signaling pathway and glutathione (GSH) metabolism signaling pathway. The related genes in the ferroptosis signaling pathway included the up-regulated gene heme oxygenase-1 (HO-1) and the down-regulated gene solute carrier family 7 member 11 (SLC7A11). The related genes in the p53 signaling pathway included the up-regulated gene tumor suppressor gene p53 and the down-regulated gene murine double minute 2 (MDM2). The related gene in the GSH metabolic signaling pathway was up-regulated gene glutaredoxin 1 (Grx1). The light microscope showed that the pulmonary alveolar structure of the normoxia group was normal. In the HALI group, the pulmonary alveolar septum widened and thickened, and the alveolar cavity shrank or disappeared. RT-RCR and Western blotting confirmed that compared with the normoxia group, the mRNA and protein expressions of HO-1 and p53 in lung tissue of the HALI group were significantly increased [HO-1 mRNA (2-ΔΔCt): 2.16±0.17 vs. 1.00±0.00, HO-1 protein (HO-1/ß-actin): 1.05±0.01 vs. 0.79±0.01, p53 mRNA (2-ΔΔCt): 2.52±0.13 vs. 1.00±0.00, p53 protein (p53/ß-actin): 1.12±0.02 vs. 0.58±0.03, all P < 0.05], and the mRNA and protein expressions of Grx1, MDM2, SLC7A11 were significantly decreased [Grx1 mRNA (2-ΔΔCt): 0.53±0.05 vs. 1.00±0.00, Grx1 protein (Grx1/ß-actin): 0.54±0.03 vs. 0.93±0.01, MDM2 mRNA (2-ΔΔCt): 0.48±0.03 vs. 1.00±0.00, MDM2 protein (MDM2/ß-actin): 0.57±0.02 vs. 1.05±0.01, SLC7A11 mRNA (2-ΔΔCt): 0.50±0.06 vs. 1.00±0.00, SLC7A11 protein (SLC7A11/ß-actin): 0.72±0.03 vs. 0.98±0.01, all P < 0.05]. CONCLUSIONS: HALI is closely related to ferroptosis, p53 and GSH metabolism signaling pathways. Targeting the key targets in ferroptosis, p53 and GSH metabolism signaling pathways may be an important strategy for the prevention and treatment of HALI.
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Lesão Pulmonar Aguda , Hiperóxia , Ratos , Camundongos , Masculino , Animais , Proteína Supressora de Tumor p53 , Hiperóxia/complicações , Ratos Sprague-Dawley , Actinas , Camundongos Endogâmicos C57BL , Transdução de Sinais , Perfilação da Expressão Gênica , RNA MensageiroRESUMO
[This corrects the article DOI: 10.3389/fmicb.2023.1197970.].
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Purpose: To investigate the clinical value of adding Jin-gu-lian (JGL) capsules into rheumatoid arthritis (RA) treatment by examining its impact on disease activity and quality of life (QoL) through a real-world study (RWS). Patients and methods: RWS was conducted to compare the inflammatory markers, including IgM-RF, ESR, and CRP, between RA patients treated with only Western medicine (reference group) and Western medicine plus JGL (study group) during one-year follow-up. The clinical data was acquired from the hospital information system (HIS). Telephone call-based follow-up on QoL (SF-36) and accompanying symptoms, including gastrointestinal complaints, attacks of pneumonia, herpes zoster, URTIs, UTIs, and LTBIs. Finally, the anti-rheumatic drugs given to both groups were also compared. RWS was further validated for its feasibility by performing studies with hydroxychloroquine (HCQ) treatment, which is a commonly used anti-rheumatic drug for RA with mild effect. Results: The study group failed to show a significant effect on inflammatory markers, especially on the CRP levels, indicating no additional clinical value of supplementing with JGL. Similarly, at the endpoint, no significant differences between the two groups on QoL and related symptoms were observed. Our study suggests that the patients in the study group might need more anti-rheumatic drugs to fill the treatment insufficiency, and the application ratio of NSAIDs would be significantly higher than the reference group. By conducting this study on HCQ treatment, the positive aspects of controlling disease activity and reducing NSAIDs application were found, which demonstrates the utility of performing the RWS to evaluate the effect of JGL. Conclusion: Adding JGL did not significantly improve the clinical efficacy of RA treatment by this RWS. Folk herbal prescriptions such as JGL are suggested to underwent strict clinical trials before application.
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OBJECTIVE: To investigate the effect of hyperoxia on intestinal metabolomics in mice. METHODS: Sixteen 8-week-old male C57BL/6 mice were randomly divided into hyperoxia group and control group, with 8 mice in each group. The hyperoxia group was exposed to 80% oxygen for 14 days. Mice were anesthetized and euthanized, and cecal contents were collected for untargeted metabolomics analysis by liquid chromatography-mass spectrometry (LC-MS) combined detection. Orthogonal partial least square discriminant analysis (OPLS-DA), volcano plot analysis, heat map analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the effects of hyperoxia on metabolism. RESULTS: (1) OPLS-DA analysis showed that R2Y was 0.967 and Q2 was 0.796, indicating that the model was reliable. (2) Volcano plot and heat map analysis showed significant statistical differences in the expression levels of metabolites between the two groups, with 541 up-regulated metabolites, 64 down-regulated metabolites, and 907 no differences, while the elevated 5-hydroxy-L-lysine was the most significant differential metabolite induced by high oxygen. (3) KEGG pathway enrichment analysis showed that porphyrin and chlorophyll metabolism (P = 0.005), lysine degradation (P = 0.047), and aromatic compound degradation (P = 0.024) were the targets affected by hyperoxia. (4) Differential analysis of metabolic products through KEGG enrichment pathway showed that hyperoxia had a significant impact on the metabolism of porphyrin and chlorophyll, lysine, and aromatic compounds such as benzene and o-cresol. CONCLUSIONS: Hyperoxia significantly induces intestinal metabolic disorders. Hyperoxia enhances the metabolism of porphyrins and chlorophyll, inhibits the degradation of lysine, and delays the degradation of aromatic compounds such as benzene and o-cresol.
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Hiperóxia , Doenças Metabólicas , Porfirinas , Camundongos , Masculino , Animais , Lisina , Benzeno , Camundongos Endogâmicos C57BL , Oxigênio , Clorofila , Biomarcadores/metabolismoRESUMO
OBJECTIVES: To examine the current situation of potentially inappropriate medicines (PIM) for treatment of chronicity in older patients and whether the inappropriate medicines were included in the 22nd World Health Organization (WHO) Model List of Essential Medicines (EMLs), China National Model list of Essential Medicines (China EMLs), or supplementary list of essential medicines in Guizhou Province 2018 (Guizhou EMLs) through real world data, so as to promote the development of lists of essential medicines suitable for older patients and provide a reference for the revision of lists of essential medicines to reduce adverse effects, drug-induced diseases and even possible death due to use of inappropriate medicines existing in lists of essential medicines. METHODS: A retrospectively study was conducted. Dispensing records of patients aged ≥ 65 admitted to convenience clinic of a tertiary hospital from January 1, 2021 to December 31, 2021 were extracted through electronic information system. Then, we merged dispensing records of the same patient on the same date as one record and patients with at least one chronic disease were included. The American Geriatrics Society(AGS)/Beers Criteria 2019 (Beers 2019) was used to evaluate the PIM status. Thereafter, the inappropriate medicines were compared with WHO EMLs, China EMLs, and Guizhou EMLs to find out percentages of drugs of PIMs existing in above lists of essential medicines in all drugs of PIMs. The above evaluation was conducted using Excel software (version 2019). RESULTS: A total of 5314 dispensing reports were included in this study. 5.95% (316/5314), 7.88% (419/5314) of PIMs met Table 2 (medicines that are potentially inappropriate in most older adults), Table 4 (medicines that should be used with caution) of Beers 2019, respectively. Among PIM drugs which met Table 2 of Beers 2019, 47.37%, 78.95%, and 78.95% were respectively included in WHO EMLs, China EMLs, and Guizhou EMLs, and that was 47.06%, 76.47%, and 82.35% for Table 4 of Beers 2019. CONCLUSIONS: PIM in older patients is common in clinical practice. Patients with diabetes, hypertension, arthritis, depression and/or anxiety and Parkinson' diseases were more frequently prescribed drugs of PIM according to Beers 2019. Take older patients into consideration and formulate List of essential medicines special for older patients may be a key way to reduce PIM.
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Prescrição Inadequada , Doença de Parkinson , Humanos , Idoso , Estudos Retrospectivos , Estudos Transversais , Lista de Medicamentos Potencialmente Inapropriados , Prescrições , Doença CrônicaRESUMO
BACKGROUND: Central venous catheters (CVCs) often cause life-threatening complications, especially CVC-related bloodstream infection (CVC-BSI) and catheter-related thrombosis (CRT). Here, we report an unusual case of misplaced CVC-induced emphysematous thrombophlebitis, a rare but potentially lethal form of CRT and CVC-BSI characterized by both thrombosis and gas formation. CASE SUMMARY: A 48-year-old male presented to the emergency room of a local hospital with sudden-onset headache and coma for 4 h. Computed tomography (CT) revealed right basal ganglia hemorrhage, so emergency decompressive craniotomy was performed and a CVC was inserted through the right subclavian vein for fluid resuscitation during anesthesia. Two days later, the patient was transferred to the intensive care unit of our hospital for further critical care. On day 9 after CVC insertion, the patient suddenly developed fever and hypotension. Point-of-care ultrasound (POCUS) demonstrated thrombosis and dilatation of the right internal jugular vein (IJV) filled with thrombosis. Ultrasonography also revealed that the CVC tip had been misplaced into the IJV and was surrounded by gas bubbles, which manifested as hyperechoic lines with dirty shadowing and comet-tail artifacts. Further CT scan confirmed air bubbles surrounding the CVC in the right neck. The final diagnosis was septic emphysematous thrombophlebitis induced by a misplaced CVC and ensuing septic shock. The responsible CVC was removed immediately. The patient received fluid resuscitation, intravenous noradrenaline, and a 10-d ultra-broad spectrum antibiotic treatment to combat septic shock. Both CVC and peripheral venous blood cultures yielded methicillin-resistant Staphylococcus cohnii. The patient was gradually weaned off vasopressors and the symptoms of redness and swelling in the right neck subsided within 7 d. CONCLUSION: Emphysematous thrombophlebitis is a fulminant and life-threatening CVC-BSI associated with thrombosis and gas formation in the vein. A misplaced CVC may facilitate the development of emphysematous thrombophlebitis. POCUS can easily identify the artifacts produced by gas and thrombosis, facilitating rapid diagnosis at the bedside.
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BACKGROUND: Severe infection often results in bacteremia, which significantly increases mortality rate. Different therapeutic strategies are employed depending on whether the blood-borne infection is Gram-negative (G-) or Gram-positive (G+). However, there is no risk prediction model for assessing whether bacteremia patients are infected with G- or G+ pathogens. AIM: To establish a clinical prediction model to distinguish G- from G+ infection. METHODS: A total of 130 patients with positive blood culture admitted to a single intensive care unit were recruited, and Th1 and Th2 cytokine concentrations, routine blood test results, procalcitonin and C-reactive protein concentrations, liver and kidney function test results and coagulation function were compared between G+ and G- groups. Least absolute shrinkage and selection operator (LASSO) regression analysis was employed to optimize the selection of predictive variables by running cyclic coordinate descent and K-fold cross-validation (K = 10). The predictive variables selected by LASSO regression analysis were then included in multivariate logistic regression analysis to establish a prediction model. A nomogram was also constructed based on the prediction model. Calibration chart, receiver operating characteristic curve and decision curve analysis were adopted for validating the prediction model. RESULTS: Age, plasma interleukin 6 (IL-6) concentration and plasma aspartate aminotransferase concentration were identified from 57 measured variables as potential factors distinguishing G+ from G- infection by LASSO regression analysis. Inclusion of these three variables in a multivariate logistic regression model identified age and IL-6 as significant predictors. In receiver operating characteristic curve analysis, age and IL-6 yielded an area under the curve of 0.761 and distinguished G+ from G- infection with specificity of 0.756 and sensitivity of 0.692. Serum IL-6 and IL-10 levels were upregulated by more than 10-fold from baseline in the G- bacteremia group but by less than ten-fold in the G+ bacteremia group. The calibration curve of the model and Hosmer-Lemeshow test indicated good model fit (P > 0.05). When the decision curve analysis curve indicated a risk threshold probability between 0% and 68%, a nomogram could be applied in clinical settings. CONCLUSION: A simple prediction model distinguishing G- from G+ bacteremia can be constructed based on reciprocal association with age and IL-6 level.
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BACKGROUND: Pacemaker lead-induced heart perforation is a rare but life-threatening complication of pacemaker implantation, and timely diagnosis remains a challenge for clinicians. Here, we report a case of pacemaker lead-induced cardiac perforation rapidly diagnosed by a "bow-and-arrow" sign on point-of-care ultrasound (POCUS). CASE SUMMARY: A 74-year-old Chinese woman who had undergone permanent pacemaker implantation 26 d before suddenly developed severe dyspnea, chest pain, and hypotension. The patient had received emergency laparotomy for an incarcerated groin hernia and was transferred to the intensive care unit 6 d before. Computed tomography was not available due to unstable hemodynamic status, so POCUS was performed at the bedside and revealed severe pericardial effusion and cardiac tamponade. Subsequent pericardiocentesis yielded a large volume of bloody pericardial fluid. Further POCUS by an ultrasonographist revealed a unique "bow-and-arrow" sign indicating right ventricular (RV) apex perforation by the pacemaker lead, which facilitated the rapid diagnosis of lead perforation. Given the persistent drainage of pericardial bleeding, urgent off-pump open chest surgery was performed to repair the perforation. However, the patient died of shock and multiple organ dysfunction syndrome within 24 h post-surgery. In addition, we also performed a literature review on the sonographic features of RV apex perforation by lead. CONCLUSION: POCUS enables the early diagnosis of pacemaker lead perforation at the bedside. A step-wise ultrasonographic approach and the "bow-and-arrow" sign on POCUS are helpful for rapid diagnosis of lead perforation.
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Background: Inhaled oxygen is the first-line therapeutic approach for maintaining tissue oxygenation in critically ill patients, but usually exposes patients to damaging hyperoxia. Hyperoxia adversely increases the oxygen tension in the gut lumen which harbors the trillions of microorganisms playing an important role in host metabolism and immunity. Nevertheless, the effects of hyperoxia on gut microbiome and metabolome remain unclear, and metagenomic and metabolomics analysis were performed in this mouse study. Methods: C57BL/6 mice were randomly divided into a control (CON) group exposed to room air with fractional inspired oxygen (FiO2) of 21% and a hyperoxia (OXY) group exposed to FiO2 of 80% for 7 days, respectively. Fecal pellets were collected on day 7 and subjected to metagenomic sequencing. Another experiment with the same design was performed to explore the impact of hyperoxia on gut and serum metabolome. Fecal pellets and blood were collected and high-performance liquid chromatography with mass spectrometric analysis was carried out. Results: At the phylum level, hyperoxia increased the ratio of Firmicutes/Bacteroidetes (p = 0.049). At the species level, hyperoxia reduced the abundance of Muribaculaceae bacterium Isolate-037 (p = 0.007), Isolate-114 (p = 0.010), and Isolate-043 (p = 0.011) etc. Linear discriminant analysis effect size (LEfSe) revealed that Muribaculaceae and Muribaculaceae bacterium Isolate-037, both belonging to Bacteroidetes, were the marker microbes of the CON group, while Firmicutes was the marker microbes of the OXY group. Metagenomic analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Carbohydrate-Active enZYmes (CAZy) revealed that hyperoxia provoked disturbances in carbohydrate and lipid metabolism. Fecal metabolomics analysis showed hyperoxia reduced 11-dehydro Thromboxane B2-d4 biosynthesis (p = 1.10 × 10-11). Hyperoxia blunted fecal linoleic acid metabolism (p = 0.008) and alpha-linolenic acid metabolism (p = 0.014). We showed that 1-docosanoyl-glycer-3-phosphate (p = 1.58 × 10-10) was the most significant differential serum metabolite inhibited by hyperoxia. In addition, hyperoxia suppressed serum hypoxia-inducible factor-1 (HIF-1, p = 0.007) and glucagon signaling pathways (p = 0.007). Conclusion: Hyperoxia leads to gut dysbiosis by eliminating beneficial and oxygen strictly intolerant Muribaculaceae with genomic dysfunction of carbohydrate and lipid metabolism. In addition, hyperoxia suppresses unsaturated fatty acid metabolism in the gut and inhibits the HIF-1 and glucagon signaling pathways in the serum.
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Inhibition of type II alveolar epithelial (AE-II) cell apoptosis is a critical way to cure hyperoxia-induced acute lung injury (HALI). It has been reported that miR-21-5p could reduce H2O2-induced apoptosis in AE-II cells. However, the upstream molecular mechanism remains unclear. Herein, we established a cellular model of HALI by exposing AE-II cells to H2O2 treatment. It was shown that miR-21-5p alleviated H2O2-induced apoptosis in AE-II cells. ROS inhibition decreased apoptosis of H2O2-evoked AE-II cells via increasing miR-21-5p expression. In addition, ROS induced MAPK and STAT3 phosphorylation in H2O2-treated AE-II cells. MAPK inactivation reduces H2O2-triggered AE-II cell apoptosis. MAPK activation inhibits miR-21-5p expression by promoting STAT3 phosphorylation in H2O2-challenged AE-II cells. Furthermore, STAT3 activation eliminated MAPK deactivation-mediated inhibition on the apoptosis of AE-II cells under H2O2 condition. In conclusion, ROS-mediated MAPK activation promoted H2O2-triggered AE-II cell apoptosis by inhibiting miR-21-5p expression via STAT3 phosphorylation, providing novel targets for HALI treatment.
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Lesão Pulmonar Aguda , Apoptose , Hiperóxia , MicroRNAs , Humanos , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/patologia , Células Epiteliais Alveolares/metabolismo , Peróxido de Hidrogênio/metabolismo , Hiperóxia/complicações , MicroRNAs/genética , MicroRNAs/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismoRESUMO
BACKGROUND: Many genetic and metabolic diseases affect the liver, but diagnosis can be difficult because these diseases may have complex clinical manifestations and diverse clinical patterns. There is also incomplete clinical knowledge of these many different diseases and limitations of current testing methods. CASE SUMMARY: We report a 53-year-old female from a rural area in China who was hospitalized for lower limb edema, abdominal distension, cirrhosis, and hypothyroidism. We excluded the common causes of liver disease (drinking alcohol, using traditional Chinese medicines, hepatitis virus infection, autoimmunity, and hepatolenticular degeneration). When she was 23-years-old, she developed night-blindness that worsened to complete blindness, with no obvious cause. Her parents were first cousins, and both were alive. Analysis of the patient's family history indicated that all 5 siblings had night blindness and impaired vision; one sister was completely blind; and another sister had night-blindness complicated with cirrhosis and subclinical hypothyroidism. Entire exome sequencing showed that the patient, parents, and siblings all had mutations in the cytochrome P450 4V2 gene (CYP4V2). The CYP4V2 mutations of the parents and two sisters were heterozygous, and the others were homozygous. Two siblings also had heterozygous dual oxidase activator 2 (DUOXA2) mutations. CONCLUSION: Mutations in the CYP4V2 gene may affect lipid metabolism and lead to chronic liver injury, fibrosis, and cirrhosis.
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OBJECTIVE: To explore whether microRNA-21-5p (miR-21-5p) has the effect of anti-apoptosis of human alveolar type II epithelial cells (AT II). METHODS: AT II cells derived from the human were cultured in vitro and used for experiments when the cells were grown until the presence of lamellar bodies and microvilli were observed by light microscope. The cells were divided into blank control group (direct culture), hydrogen peroxide (H2O2) injury group (cultured with 0.5 mmol/L H2O2), and miR-21-5p overexpression group (using miR-21-5p with a multiplicity of infection (MOI) of 100 lentiviral overexpression vector with 0.5 mmol/L H2O2) and miR-21-5p empty virus control group (miR-21-5p lentiviral blank vector was co-cultured with 0.5 mmol/L H2O2). In each group, cell proliferation was detected by cell counting kit-8 (CCK-8) at 0, 12, 24, 36, and 48 hours of cell culture; cell apoptosis was detected by flow cytometry at 24 hours of culture. RESULTS: (1) Cell proliferation activity test results: with the extension of cell culture time, the cell proliferation activity of the blank control group gradually increased, while the cell proliferation activity gradually decreased after the addition of 0.5 mmol/L H2O2. However, the cells proliferation activity in the miR-21-5p overexpression group decreased more slowly than that in the H2O2 injury group and the miR-21-5p empty virus control group, and the cell proliferation activity at 48 hours was significantly higher than the H2O2 injury group and the miR-21-5p empty virus control group (A value: 0.295±0.005 vs. 0.184±0.005, 0.169±0.002, both P < 0.05). It showed that both H2O2 and lentivirus accelerated cell damage, while miR-21-5p could reduce cell apoptosis. (2) Apoptosis rate test results: compared with the blank control group, the apoptosis rate increased significantly after adding 0.5 mmol/L H2O2; while the apoptosis rate of the miR-21-5p overexpression group was lower than that of the H2O2 injury group and miR-21-5p empty virus control group [early apoptosis rate: (14.31±0.12)% vs. (24.50±0.12)%, (23.41±0.13)%; late apoptosis rate: (8.12±0.13)% vs. (9.71±0.11)%, (10.41±0.15)%; overall apoptosis rate: (22.33±0.12)% vs. (34.21±0.10)%, (33.82±0.14)%; all P < 0.05], which further proved that miR-21-5p had anti-apoptotic effects. CONCLUSIONS: miR-21-5p has an anti-apoptotic effect on human AT II.
Assuntos
Células Epiteliais Alveolares , MicroRNAs , Apoptose , Proliferação de Células , Humanos , Peróxido de Hidrogênio , MicroRNAs/genéticaRESUMO
BACKGROUND: Emphysematous pyelonephritis (EPN) is a rare but fatal necrotic infection of the kidney, which usually leads to septic shock. Therefore, early diagnosis and optimized therapy are of paramount importance. In the past two decades, point-of-care ultrasound (POCUS) has been widely used in clinical practice, especially in emergency and critical care settings, and helps to rapidly identify the source of infection in sepsis. We report a rare case in which a "falls" sign on POCUS played a pivotal role in the early diagnosis of EPN. CASE SUMMARY: A 57-year-old man presented with fever and lumbago for 3 d prior to admission. He went to the emergency room, and the initial POCUS detected gas bubbles in the hepatorenal space showing a hyperechoic focus with dirty shadowing and comet-tail artifacts. This imaging feature was like a mini waterfall. His blood and urine culture demonstrated Escherichia coli bacteremia, and EPN associated with septic shock was diagnosed. The patient did not respond to broad-spectrum antibiotic treatment and a perirenal abscess developed. He subsequently underwent computed tomography-guided percutaneous catheter drainage, and fully recovered. We also review the literature on the sonographic features of POCUS in EPN. CONCLUSION: This case indicates that a "falls" sign on POCUS facilitates the rapid diagnosis of severe EPN at the bedside.
RESUMO
Background: Oxygen therapy usually exposes patients to hyperoxia, which induces injuries in the lung, the heart, and the brain. The gut and its microbiome play key roles in critical illnesses, but the impact of hyperoxia on the gut and its microbiome remains not very clear. We clarified the time- and dose-dependent effects of hyperoxia on the gut and investigated oxygen-induced gut dysbiosis and explored the underlying mechanism of gut injury by transcriptome analysis. Methods: The C57BL/6 mice were randomly divided into the control group and nine different oxygen groups exposed to hyperoxia with an inspired O2 fraction (FiO2) of 40, 60, and 80% for 24, 72, and 168 h (7 days), respectively. Intestinal histopathological and biochemical analyses were performed to explore the oxygen-induced gut injury and inflammatory response. Another experiment was performed to explore the impact of hyperoxia on the gut microbiome by exposing the mice to hyperoxia (FiO2 80%) for 7 days, with the 16S rRNA sequencing method. We prolonged the exposure (up to 14 days) of the mice to hyperoxia (FiO2 80%), and gut transcriptome analysis and western blotting were carried out to obtain differentially expressed genes (DEGs) and signaling pathways related to innate immunity and cell death. Results: Inhaled oxygen induced time- and dose-dependent gut histopathological impairment characterized by mucosal atrophy (e.g., villus shortening: 80% of FiO2 for 24 h: P = 0.008) and enterocyte death (e.g., apoptosis: 40% of FiO2 for 7 days: P = 0.01). Administered time- and dose-dependent oxygen led to intestinal barrier dysfunction (e.g., endotoxemia: 80% of FiO2 for 72 h: P = 0.002) and potentiated gut inflammation by increasing proinflammatory cytokines [e.g., tumor necrosis factor alpha (TNF-α): 40% of FiO2 for 24 h: P = 0.003)] and reducing anti-inflammatory cytokines [Interleukin 10 (IL-10): 80% of FiO2 for 72 h: P < 0.0001]. Hyperoxia induced gut dysbiosis with an expansion of oxygen-tolerant bacteria (e.g., Enterobacteriaceae). Gut transcriptome analysis identified 1,747 DEGs and 171 signaling pathways and immunoblotting verified TLR-4, NOD-like receptor, and apoptosis signaling pathways were activated in oxygen-induced gut injury. Conclusions: Acute hyperoxia rapidly provokes gut injury in a time- and dose-dependent manner and induces gut dysbiosis, and an innate immune response is involved in an oxygen-induced gut injury.
RESUMO
BACKGROUND: Fulminant lupus myocarditis is a rare but fatal manifestation of systemic lupus erythematosus. Aggressive immunosuppressive treatments are important in its successful management. However, they can significantly damage the immunity and are associated with a considerable risk of infection development and spread. We present a rare and complicated case of a 20-year-old female diagnosed with fulminant lupus myocarditis accompanied by pneumonia. The patient was successfully treated with plasma exchange (PE) for fulminant lupus myocarditis. CASE SUMMARY: A 20-year-old Chinese woman presented to the Hematology Department complaining of fatigue and knee pain. Blood test showed anemia and thrombocytopenia. On the second day of hospitalization, she was transferred to the ICU due to dyspnea and hypotension. Autoimmune profiles showed hypocomplementemia and positive antinuclear antibodies. Computer tomography showed an enlarged heart and pneumonia. Ultrasound revealed an enlarged heart with a low left ventricular ejection fraction. Fulminant lupus myocarditis with cardiogenic shock was initially considered. Due to the accompanying pneumonia, aggressive immunosuppression was contraindicated. Her cardiac function remained critical after the initial therapy of intravenous immunoglobulin and corticosteroids at a conventional dose, but she responded well to later PE therapy plus corticosteroids administration. The patient fully recovered with normal cardiac function. CONCLUSION: This case indicates that PE is a valuable treatment choice without adverse effects of immunosuppression in patients with fulminant lupus myocarditis and coexisting infection.