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OBJECTIVE: This meta-analysis aimed to investigate the efficacy and safety of potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) in treating erosive esophagitis (EE). METHODS: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched using predefined search terms up to January 2024. Relevant randomized controlled trials were included. The outcoming were the EE healing rate and treatment-related adverse events incidence. RESULTS: Nine randomized controlled trials involving 4012 patients were included. Patients receiving P-CAB exhibited a significantly better overall healing rate compared with PPI at week 2 [risk ratio (RR) = 1.06], but no statistical difference was observed at week 4 and week 8. Subgroup analysis revealed that P-CAB demonstrated a higher healing rate for patients with Los Angeles (LA) grade C/D, regardless of the assessment at week 2 (RR = 1.17), week 4 (RR = 1.10), or week 8 (RR = 1.08). However, no significant difference was found between PPI and P-CAB for patients with LA grade A/B at week 2, week 4, or week 8. Furthermore, patients treated with P-CAB had lower recurrence rates during maintenance therapy compared with PPI (RR = 0.79). In terms of safety, P-CAB was associated with a lower incidence of headache compared with PPI (RR = 0.32), with no statistical difference found in any treatment-related adverse events between the two groups. CONCLUSIONS: P-CAB was found to be safe and effective for EE treatment compared with PPI, particularly in 2-week short-term treatment, severe EE (LA grade C/D) treatment, or maintenance therapy. Limitations such as potential heterogeneity among included trials should be considered in the interpretation of these findings.
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BACKGROUND: This meta-analysis aims to investigate the efficacy and safety of programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) combined with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors for patients with advanced or metastatic non-small cell lung cancer (NSCLC). METHODS: Authors conducted a comprehensive search of PubMed, Embase, Cochrane Library, Web of Science, Scopus, and Medline for randomized controlled trials comparing the prognosis and safety of PD-1/PD-L1 plus CTLA-4 inhibitors with other therapies for advanced or metastatic NSCLC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effect sizes. The primary outcomes of this study were overall survival (OS) and progression-free survival. RESULTS: A total of 4943 patients diagnosed with stage III/IV advanced or metastatic NSCLC were included in the analysis of the 6 randomized controlled trials. The results showed that patients receiving dual immunotherapy with PD-1/PD-L1 plus CTLA-4 inhibitors had a longer survival time compared with the control group (HR = 0.88, P = 0.044). However, no statistically significant difference was observed in progression-free survival (HR = 0.95, P = 0.579). Subgroup analysis revealed better OS in the interventional group for patients aged >65 years (HR = 0.88, P = 0.076), smokers (HR = 0.81, P = 0.036), and those with a tumor mutational burden (TMB) ≥20 mut/Mb (HR = 0.66, P < 0.001). Conversely, the control group demonstrated superior OS in patients with TMB <20 mut/Mb (HR = 1.14, P = 0.048). In addition, the statistical results indicated a lower incidence rate of any-grade anemia in the dual immunotherapy group compared with the control group (RR = 0.32, P = 0.04). CONCLUSIONS: This meta-analysis demonstrates the effectiveness and safety of dual immunotherapy with PD-1/PD-L1 plus CTLA-4 inhibitors for treating advanced or metastatic NSCLC. Its efficacy is influenced by certain clinical and pathological factors, such as age, smoking status, and TMB.
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Antígeno B7-H1 , Antígeno CTLA-4 , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Receptor de Morte Celular Programada 1 , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Antígeno CTLA-4/antagonistas & inibidores , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Antígeno B7-H1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodosRESUMO
Hg(I) may control Hg redox kinetics; however, its metastable nature hinders analysis. Herein, the stability of Hg(I) during standard preparation and analysis was studied. Gravimetric analysis showed that Hg(I) was stable in its stock solution (1000 mg L-1), yet completely disproportionated when its dilute solution (10 µg L-1) was analyzed using liquid chromatography (LC)-ICPMS. The Hg(I) dimer can form through an energetically favorable comproportionation between Hg(0) and Hg(II), as supported by density functional theory calculation and traced by the rapid isotope exchange between 199Hg(0)aq and 202Hg(II). However, the separation of Hg(0) and Hg(II) (e.g., LC process) triggered its further disproportionation. Polypropylene container, increasing headspace, decreasing pH, and increasing dissolved oxygen significantly enhanced the disproportionation or redox transformations of Hg(I). Thus, using a glass container without headspace and maintaining a slightly alkaline solution are recommended for the dilute Hg(I) stabilization. Notably, we detected elevated concentrations of Hg(I) (4.4-6.1 µg L-1) in creek waters from a heavily Hg-polluted area, accounting for 54-70% of total dissolved Hg. We also verified the reductive formation of Hg(I) in Hg(II)-spiked environmental water samples, where Hg(I) can stably exist in aquatic environments for at least 24 h, especially in seawater. These findings provide mechanistic insights into the transformation of Hg(I), which are indicative of its further environmental identification.
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Mercúrio , Poluentes Químicos da Água , Mercúrio/análise , Água do Mar/análise , Água do Mar/química , Isótopos/análise , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: Preference-based measures of health-related quality of life (HRQoL), such as the EQ-5D or the SF-6D, are essential for health economic evaluation. However, they are rarely included in clinical trials of ankylosing spondylitis (AS). This study aims to develop mapping algorithms to predict EQ-5D-3L and EQ-5D-5L health utility scores from the Bath Ankylosing Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI). METHODS: Patients with AS were recruited from the largest tertiary hospital in Shandong province, China, between December 2019 and October 2020. Patients were selected by convenience sampling method according to the following criteria: (1) diagnosed with AS according to the New York criteria; (2) aged 18 years and above; and (3) without mental disorders; (4) able to understand the questionnaires; (5) without serious complications. There were 243 patients who completed the face-to-face questionnaire survey, and 5 cases with missing values in key variables were excluded. Ordinary least squares, censored least absolute deviations, Tobit, adjusted limited dependent variable mixture model and beta-mixture model (BM) in the direct approach and ordered logit and multinomial logit (Mlogit) model in the response approach were used to develop mapping algorithms. Mean absolute error, root mean square error, Spearman's correlation coefficient and concordance correlation coefficient were used to access predictive performance. RESULTS: The 238 patients with AS had a mean age of 35.19 (SD = 9.59) years, and the majority (74.47%) were male. The observed EQ-5D-3L and EQ-5D-5L health utility values were 0.88 (SD = 0.12) and 0.74 (SD = 0.27), respectively. The EQ-5D-5L had higher conceptual overlap with the BASDAI and BASFI than the EQ-5D-3L did. The Mlogit was the best-performing model for the EQ-5D-3L, and the BM showed better performance in predicting EQ-5D-5L than other direct and indirect mapping models did. CONCLUSION: This study demonstrates that the EQ-5D-5L, rather than EQ-5D-3L, should be selected as the target outcome measure of HRQoL in patients with AS in China, and the BM mapping algorithm could be used to predict EQ-5D-5L values from BASDAI and BASFI for health economic evaluation.
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Algoritmos , Qualidade de Vida , Índice de Gravidade de Doença , Espondilite Anquilosante , Humanos , Espondilite Anquilosante/psicologia , Espondilite Anquilosante/fisiopatologia , Masculino , Feminino , Adulto , Inquéritos e Questionários/normas , China , Pessoa de Meia-IdadeRESUMO
BACKGROUND: This study aims to investigate the effect of PD-1/PD-L1 immunotherapy on cardiac-related adverse events in patients with advanced or metastatic lung cancer. METHODS: We conducted a detailed search in PubMed, Web of Science, Cochran, and Embase for articles on the application of immunotherapy for lung cancer and report cardiac-related adverse events with respect to myocardial ischemia, pericardial effusion, myocarditis, and electrophysiology. The dichotomous variables were assessed by relative risk (RR) and 95% confidence intervals (CI). RESULTS: A total of 7132 subjects were included in 12 phase III randomized controlled trials (RCTs). The results showed that under the fixed effects model, the probability of cardiac-related adverse events in pericardial effusion was higher in the experimental group than in the control group (RR 2.30, 95% CI 1.01-5.21, P = 0.05). Under the random effects model, there was no statistical difference between the two groups (RR 2.03, 95% CI 0.81-5.12, P = 0.13). No statistical difference is observed between the experimental group and the control group (under the fixed effects model and the random effects model) for other cardiac-related adverse events, including myocarditis, acute coronary syndrome, myocardial infarction, acute myocardial infarction, myocardial ischemia, unstable angina, ventricular tachycardia, supraventricular tachycardia, tachycardia, bradycardia, atrial flutter, atrial fibrillation, cardiac failure, cardiac arrest, cardiopulmonary failure, acute heart failure, cardiac arrest (all P > 0.05). CONCLUSIONS: PD-1/PD-L1 immunotherapy in advanced or metastatic lung cancer is generally safe for cardiac-related adverse events.
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Insuficiência Cardíaca , Neoplasias Pulmonares , Isquemia Miocárdica , Miocardite , Derrame Pericárdico , Humanos , Receptor de Morte Celular Programada 1 , Antígeno B7-H1 , Neoplasias Pulmonares/terapia , Imunoterapia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: While ondansetron (OND) is widespread availability, the contribution of OND to improve patient outcomes among intensive care unit (ICU) patients has not been examined. This study aimed to illustrate the association between early OND use and in-hospital mortality in critically ill patients and investigate whether this association differed according to OND dose. METHODS: The MIMIC-IV database was employed to identify patients who had and had not received OND. Statistical approaches included multivariate logistic regression, propensity score matching (PSM), and propensity score-based inverse probability of treatment weighting (IPTW) models to ensure the robustness of our findings. RESULTS: In total, 51,342 ICU patients were included. A significant benefit in terms of in-hospital mortality was observed in the OND patients compared to the non-OND group in the early stage [odds ratio (OR) = 0.75, 95% CI 0.63-0.89, p < 0.001]. In the circulatory system group, the early OND administration was associated with improved in-hospital mortality in ICU patients (OR 0.48, 95% CI 0.34-0.66; P < 0.001). The risk of in-hospital mortality was also lower in early OND users than in non-OND users both in the medical admission group and the surgical ICU admission group, and ORs were 0.57 (95% CI 0.42-0.76; P < 0.001) and 0.79 (95% CI 0.62-0.91; P < 0.001), respectively. A positive role of daily low- and moderate-dose OND treatment in early-stage was showed on the in-hospital mortality in PSM cohort, and the ORs were 0.75 (95% CI 0.62-0.90; P < 0.001) and 0.63 (95% CI 0.43-0.91; P < 0.001), respectively. The relationship between the daily low- and moderate-dose of OND and in-hospital mortality was also significant in ICU patients with cardiovascular diseases, and ORs were 0.51(95% CI 0.36-0.73; P < 0.001), and 0.26(95% CI 0.11-0.65; P < 0.001), respectively. Daily low-to-moderate dose of OND was also associated with in-hospital mortality in ICU entire cohort. CONCLUSIONS: Early OND use is closely associated with lower in-hospital mortality in ICU patients. Daily low-to-moderate dose of OND application is protective against in-hospital mortality. This association is more evident in the circulatory system group.
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Estado Terminal , Ondansetron , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Ondansetron/uso terapêutico , Estudos RetrospectivosRESUMO
Exposure to ammonia can cause convulsions, coma, and death. In this study, we investigate the effects of ammonia exposure on immunoregulatory and neuroendocrine changes in Takifugu rubripes. Fish were sampled at 0, 12, 24, 48, and 96 h following exposure to different ammonia concentrations (0, 5, 50, 100, and 150 mg/L). Our results showed that exposure to ammonia significantly reduced the concentrations of C3, C4, IgM, and LZM whereas the heat shock protein 70 and 90 levels significantly increased. In addition, the transcription levels of Mn-SOD, CAT, GRx, and GR in the liver were significantly upregulated following exposure to low ammonia concertation, however, downregulated with increased exposure time. These findings suggest that ammonia poisoning causes oxidative damage and suppresses plasma immunity. Ammonia exposure also resulted in the elevation and depletion of the T3 and T4 levels, respectively. Furthermore, ammonia stress induced an increase in the corticotrophin-releasing hormone, adrenocorticotropic hormone, and cortisol levels, and a decrease in dopamine, noradrenaline, and 5-hydroxytryptamine levels in the brain, illustrating that ammonia poisoning can disrupt the endocrine and neurotransmitter systems. Our results provide insights into the mechanisms underlying the neurotoxic effects of ammonia exposure, which helps to assess the ecological and environmental health risks of this contaminant in marine fish.
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Amônia , Takifugu , Hormônio Adrenocorticotrópico/metabolismo , Amônia/metabolismo , Animais , Encéfalo/metabolismo , Dopamina/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Hidrocortisona/metabolismo , Imunidade , Imunoglobulina M/metabolismo , Neurotransmissores/metabolismo , Norepinefrina/metabolismo , Serotonina/metabolismo , Superóxido Dismutase/metabolismo , Takifugu/metabolismo , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismoRESUMO
Tiger pufferfish (Takifugu rubripes) is one of Asia's most economically valuable aquaculture species. However, winter production of this species in North China is limited by low water temperature and unavailability of high-quality feed, resulting in high mortality and low profitability. Therefore, the aim of this study was to evaluate the effect of feeding frequency (F1: one daily meal; F2: two daily meals; F3: four daily meals; F4: continuous diurnal feeding using a belt feeder) on the growth performance, plasma biochemistry, digestive and antioxidant enzyme activities, and expression of appetite-related genes in T. rubripes (initial weight: 266.80 ± 12.32 g) cultured during winter (18.0 ± 1.0 °C) for 60 days. The results showed that fish in the F3 group had the highest final weight, weight gain rate, specific growth rate, survival rate, and best feed conversion ratio. Additionally, daily feed intake increased significantly with increasing feeding frequency. The protein efficiency and lipid efficiency ratios of fish in the F3 group were significantly higher than those of fish in the other groups. Furthermore, total cholesterol, triglycerides, and glucose levels increased with increasing feeding frequency, peaking in the F2 group and decreasing under higher feeding frequencies. The antioxidant (superoxide dismutase, catalase, glutathione, and glutathione peroxidase) and digestive (trypsin, amylase, and lipase) enzyme activities of fish in the F1 group were significantly higher than those of fish in the F3 and F4 groups. Additionally, there was a decrease in orexin expression with increasing feeding frequency. In contrast, the expression levels of tachykinin, cholecystokinin, and leptin increased with increasing feeding frequency, peaking in the F4 group. Overall, the findings of this study indicated that a feeding frequency of four meals per day was optimal for improved growth performance of pufferfish juveniles cultured during winter.
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Antioxidantes , Takifugu , Animais , Takifugu/metabolismo , Catalase/genética , Catalase/metabolismo , Antioxidantes/metabolismo , Leptina/metabolismo , Orexinas/metabolismo , Orexinas/farmacologia , Apetite , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Tripsina/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Peixes/metabolismo , Triglicerídeos/metabolismo , Colesterol/metabolismo , Glutationa/metabolismo , Colecistocinina , Amilases/metabolismo , Lipase/metabolismo , Água/metabolismo , Glucose/metabolismo , Lipídeos/farmacologiaRESUMO
A simple and efficient dithizone-functionalized solid-phase extraction (SPE) procedure, online coupled with high-performance liquid chromatography (HPLC)-inductively coupled plasma mass spectrometry, was developed for the first time for enrichment and determination of ultra-trace mercury (Hg) species (inorganic divalent Hg (Hg(II)), methylmercury (CH3Hg(II)) and ethylmercury (C2H5Hg(II)) in cereals and environmental samples. In the proposed method, functionalization of the commercial C18 column with dithizone, enrichment, and elution of the above Hg species can be completed online with the developed SPE device. A simple solution of 2-mercaptoethanol (1% (V/V)) could be used as an eluent for both the SPE and HPLC separation of Hg species, significantly simplifying the method and instrumentation. The online SPE method was optimized by varying dithizone dose, 2-mercaptoethanol concentration, and sample volume. In addition, the effect of pH, coexisting interfering ions, and salt effect on the enrichment was also discussed. Under the optimized conditions, the detection limits of Hg species for 5 mL water sample were 0.15 ng/L for Hg(II), 0.07 ng/L for CH3Hg(II), and 0.04 ng/L for C2H5Hg(II) with recoveries in the range of 85%-100%. The developed dithizone-functionalized C18 SPE column can be reused after a single functionalization, which significantly simplifies the enrichment step. Moreover, the stability of Hg species enriched on the SPE column demonstrated its suitability for field sampling of Hg species for later laboratory analysis. This environment-friendly method offers a robust tool to detect ultra-trace Hg species in cereals and environmental samples.
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Mercúrio , Cromatografia Líquida de Alta Pressão , Ditizona , Grão Comestível , Extração em Fase SólidaRESUMO
Scutellaria barbata (S. barbata), a traditional herbal medicine used in southern China, possesses anti-inflammatory, antitumor, spasmolytic and expectorant effects. However, there are not many recent studies on its gastrointestinal effects. This study aimed to evaluate the antidiarrheal effect of the ethanol extract of S. barbata (SBE) and its effect on the isolated jejunum smooth muscle. METHODS: The antidiarrheal effect of SBE (doses: 125, 250 and 500 mg/kg) on castor oil-induced diarrhea was investigated in vivo. The effect of SBE (0.01-10 mg/mL) on spontaneous or acetylcholine chloride (ACh, 10µM)/KCl (60mM)-induced contraction of isolated rabbit jejunum smooth muscle was examined in vitro. The possible spasmolytic mechanism of SBE (1 and 3mg/mL) was analyzed by accumulating CaCl2 in a Ca2+-free high-K+ (60mM) solution. RESULTS: SBE (125, 250 and 500mg/kg) could delay the initial semi-solid onset time of mice and also reduce the diarrhea index in vivo. Furthermore, SBE (0.01-10mg/mL) could alleviate the spontaneous or ACh/KCl-induced contraction in vitro. SBE (1 and 3mg/mL) also inhibited the contraction induced by CaCl2, and the concentration-response curves of CaCl2 moved downward and to the right, similar to those of verapamil (0.01 and 0.1µM). CONCLUSIONS: SBE exerts antidiarrheal and spasmolytic effects, which provides a pharmacological basis for its use in functional gastrointestinal disorders.
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Antineoplásicos , Scutellaria , Animais , Antidiarreicos/uso terapêutico , Antineoplásicos/farmacologia , Cloreto de Cálcio/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Etanol/farmacologia , Jejuno , Músculo Liso , Parassimpatolíticos/farmacologia , Extratos Vegetais/uso terapêutico , CoelhosRESUMO
Lophatheri Herba is a traditional Chinese medicine, which is commonly used in the treatment of fever, stomatitis, urodynia. The aim of the study is to evaluate the antidiarrheal activity of the ethanol extract of Lophatheri Herba (Gramineae, ELH) and observe its effect on isolated jejunum smooth muscle in rabbits, so that we can provide a possible pharmacological basis for its clinical use. Methods: In vivo, the antidiarrheal activity of ELH (250, 500 and 1000 mg/kg; orally) in castor oil-induced Kun Ming mice was evaluated. In vitro, the effect of ELH (0.01-10 mg/mL) on the spontaneous and ACh (10µM)/K+ (60mM)-induced contraction of isolated rabbit jejunum smooth muscle was studied. The possible mechanism of spasmolytic effect of ELH (1, 3mg/mL) was explored by pretreatment of intestinal tract with CaCl2. Results: ELH (500 and 1000mg/kg) exhibited antidiarrheal effect and it (0.01-10 mg/mL) inhibited the spontaneous and ACh/K+-induced contraction with an EC50 value of 1.27 (0.89-1.34), 0.76 (0.54-1.02) and 0.34 (0.27-0.53), it also shifted the concentration-response curves of CaCl2 to right with decreased in max, similar to verapamil. ELH has significant antidiarrheal and spasmolytic effect, this provides the pharmacological basis for use in gastrointestinal disorders.
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Antidiarreicos , Parassimpatolíticos , Animais , Antidiarreicos/farmacologia , Cloreto de Cálcio/farmacologia , Etanol/farmacologia , Jejuno , Camundongos , Músculo Liso , Parassimpatolíticos/farmacologia , Extratos Vegetais/farmacologia , CoelhosRESUMO
BACKGROUND: COVID-19 pandemic has forced physicians to quickly determine the patient's condition and choose treatment strategies. This study aimed to build and validate a simple tool that can quickly predict the deterioration and survival of COVID-19 patients. METHODS: A total of 351 COVID-19 patients admitted to the Third People's Hospital of Yichang between 9 January to 25 March 2020 were retrospectively analyzed. Patients were randomly grouped into training (n = 246) or a validation (n = 105) dataset. Risk factors associated with deterioration were identified using univariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression. The factors were then incorporated into the nomogram. Kaplan-Meier analysis was used to compare the survival of patients between the low- and high-risk groups divided by the cut-off point. RESULTS: The least absolute shrinkage and selection operator (LASSO) regression was used to construct the nomogram via four parameters (white blood cells, C-reactive protein, lymphocyte≥0.8 × 109/L, and lactate dehydrogenase ≥400 U/L). The nomogram showed good discriminative performance with the area under the receiver operating characteristic (AUROC) of 0.945 (95% confidence interval: 0.91-0.98), and good calibration (P = 0.539). Besides, the nomogram showed good discrimination performance and good calibration in the validation and total cohorts (AUROC = 0.979 and AUROC = 0.954, respectively). Decision curve analysis demonstrated that the model had clinical application value. Kaplan-Meier analysis illustrated that low-risk patients had a significantly higher 8-week survival rate than those in the high-risk group (100% vs 71.41% and P < 0.0001). CONCLUSION: A simple-to-use nomogram with excellent performance in predicting deterioration risk and survival of COVID-19 patients was developed and validated. However, it is necessary to verify this nomogram using a large-scale multicenter study.
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COVID-19/diagnóstico , COVID-19/mortalidade , Nomogramas , Adulto , Idoso , Proteína C-Reativa/análise , China , Feminino , Hospitalização , Humanos , L-Lactato Desidrogenase/sangue , Contagem de Leucócitos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
Background: Ischemic stroke is a complex pathological process, involving inflammatory reaction, energy metabolism disorder, free radical injury, cell apoptosis and other aspects. Accumulating evidences have revealed that MFG-E8 had a protective effect on multiple organ injuries. However, the comprehensive function and mechanism of MFG-E8 in ischemic brain remain largely unclear.Methods: BV-2 cells were treated with recombinant murine MFG-E8 (rmMFG-E8) or/and Colivelin TFA after exposing for 4 h with oxygen glucose deprivation (OGD). Cell viability and apoptosis were assessed by MTT assay and Flow cytometry. RT-qPCR and Western blot assays were applied to examine the expression levels of MFG-E8, apoptosis-related proteins and M1/M2 polarization markers.Results: Our results demonstrated that OGD significantly inhibited microglial viability and facilitated apoptosis. In addition, we found that OGD downregulated MFG-E8 expression, and MFG-E8 inhibited OGD-induced microglial apoptosis and promoted microglial M2 polarization. In terms of mechanism, we proved that MFG-E8 regulated OGD-induced microglial M1/M2 polarization by inhibiting p-STAT3 and SOCS3 expressions, which was reversed by STAT3 activator (Colivelin TFA). Finally, we verified MFG-E8 alleviated OGD-induced neuronal cell apoptosis by M2 polarization of BV-2 cells.Conclusions: We demonstrated that MFG-E8 reduced neuronal cell apoptosis by enhancing activation of microglia via STAT3 signaling. Therefore, we suggested that MFG-E8 might provide a novel mechanism for ischemic stroke.
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Antígenos de Superfície/biossíntese , Hipóxia Celular/fisiologia , Glucose/deficiência , Microglia/metabolismo , Proteínas do Leite/biossíntese , Neurônios/metabolismo , Fator de Transcrição STAT3/biossíntese , Animais , Apoptose/fisiologia , Linhagem Celular , Polaridade Celular/fisiologia , Técnicas de Cocultura , Camundongos , Proteínas do Leite/antagonistas & inibidoresRESUMO
Coronavirus Disease 2019 (COVID-19) has become a pandemic since March 2020. We describe here 2 cases of COVID-19 infection in a posttransplant setting. First one is a 59-year-old renal transplant recipient; the second is a 51-year-old allogeneic bone marrow transplant recipient. Both patients were on immunosuppressant therapy and had stable graft function before COVID-19 infection. After the diagnosis of COVID-19, immunosuppressive agents were discontinued and methylprednisolone with prophylactic antibiotics were initiated, however, the lung injury progressed. The T cells were extremely low in both patients after infection. Both patients died despite the maximal mechanical ventilatory support. Therefore, the prognosis of COVID-19 pneumonia following transplantation is not optimistic and remains guarded. Lower T cell count may be a surrogate for poor outcome.
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Transplante de Medula Óssea , Infecções por Coronavirus/complicações , Falência Renal Crônica/complicações , Transplante de Rim , Leucemia Mieloide Aguda/complicações , Pneumonia Viral/complicações , Transplantados , Antibacterianos/administração & dosagem , Infecções Bacterianas/complicações , COVID-19 , China , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Infecção Hospitalar/complicações , Evolução Fatal , Humanos , Imunossupressores/administração & dosagem , Falência Renal Crônica/cirurgia , Leucemia Mieloide Aguda/terapia , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Complicações Pós-Operatórias , Prognóstico , Respiração Artificial , Linfócitos T/citologiaRESUMO
The coronavirus disease 2019 (COVID-19) has evolved into a pandemic rapidly. Most of the literature show that the elevated liver enzymes in COVID-19 are of little clinical significance. Lower albumin level is seen in severe COVID-19 and is not parallel to the changes in alanine aminotransferase and aspartate aminotransferase levels. We aimed to explore the impact of hypoalbuminemia in COVID-19. This retrospective cohort study included adult patients with confirmed COVID-19. The relationship between hypoalbuminemia and death was studied using binary logistic analysis. A total of 299 adult patients were included, 160 (53.5%) were males and the average age was 53.4 ± 16.7 years. The median time from the onset of illness to admission was 3 days (interquartile ranges, 2-5). Approximately one-third of the patients had comorbidities. Hypoalbuminemia (<35 g/L) was found in 106 (35.5%) patients. The difference in albumin was considerable between survivors and non-survivors (37.6 ± 6.2 vs 30.5 ± 4.0, P < .001). Serum albumin level was inversely correlated to white blood cell (r = -.149, P = .01) and neutrophil to lymphocyte ratio (r = -.298, P < .001). Multivariate analysis showed the presence of comorbidities (OR, 6.816; 95% CI, 1.361-34.133), lymphopenia (OR, 13.130; 95% CI, 1.632-105.658) and hypoalbuminemia (OR, 6.394; 95% CI, 1.315-31.092) were independent predictive factors for mortality. In conclusion, hypoalbuminemia is associated with the outcome of COVID-19. The potential therapeutic value of albumin infusion in COVID-19 should be further explored at the earliest.
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COVID-19/diagnóstico , Hospitalização/estatística & dados numéricos , Hipoalbuminemia/complicações , Adulto , Fatores Etários , Idoso , COVID-19/fisiopatologia , China , Comorbidade , Registros Eletrônicos de Saúde , Feminino , Humanos , Hepatopatias/sangue , Hepatopatias/complicações , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de RiscoRESUMO
Diabetic cardiomyopathy (DCM) is a condition associated with significant structural changes including cardiac tissue necrosis, localized fibrosis, and cardiomyocyte hypertrophy. This study sought to assess whether and how FBXL10 can attenuate DCM using a rat streptozotocin (STZ)-induced DCM model system. In the current study, we found that FBXL10 expression was significantly decreased in diabetic rat hearts. FBXL10 protected cells from high glucose (HG)-induced inflammation, oxidative stress, and apoptosis in vitro. In addition, FBXL10 significantly activated PKC ß2 signaling pathway in H9c2 cells and rat model. The cardiomyocyte-specific overexpression of FBXL10 at 12 weeks after the initial STZ administration attenuated oxidative stress and inflammation, thereby reducing cardiomyocyte death and preserving cardiac function in these animals. Moreover, FBXL10 protected against DCM via activation of the PKC ß2 pathway. In conclusion, FBXL has the therapeutic potential for the treatment of DCM.
Assuntos
Diabetes Mellitus Experimental/genética , Cardiomiopatias Diabéticas/genética , Proteínas F-Box/genética , Glucose/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Técnicas de Cultura de Células , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Cardiomiopatias Diabéticas/induzido quimicamente , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/fisiopatologia , Proteínas F-Box/metabolismo , Regulação da Expressão Gênica , Glucose/metabolismo , Hemodinâmica , Masculino , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Estresse Oxidativo , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , EstreptozocinaRESUMO
The gut microbiota and its short chain fatty acid (SCFA) metabolites have been established to play an important protective role against neurodegenerative diseases. Our previous study demonstrated that cerebral ischemic stroke triggers dysfunctional gut microbiota and increased intestinal permeability. In this study, we aimed to clarify the mechanism by which gut microbiota and SCFAs can treat cerebral ischemic stroke in rat middle cerebral artery occlusion models and use the information to develop new therapies. Our results show that oral administration of non-absorbable antibiotics reduced neurological impairment and the cerebral infarct volume, relieved cerebral edemas, and decreased blood lipid levels by altering the gut microbiota. We also found that ischemic stroke decreased intestinal levels of SCFAs. And that transplanting fecal microbiota rich in these metabolites was an effective means of treating the condition. Compared with other SCFAs, butyric acid showed the highest negative correlation with ischemic stroke. Supplementation with butyric acid treated models of ischemic stroke effectively by remodeling the gut microbiota, enriching the beneficial Lactobacillus, and repairing the leaky gut. In conclusion, interfering with the gut microbiota by transplanting fecal bacteria rich in SCFAs and supplementing with butyric acid were found to be effective treatments for cerebral ischemic stroke.
Assuntos
Isquemia Encefálica/microbiologia , Isquemia Encefálica/terapia , Ácido Butírico/farmacologia , Ácidos Graxos Voláteis/farmacologia , Microbioma Gastrointestinal/fisiologia , Acidente Vascular Cerebral/microbiologia , Acidente Vascular Cerebral/terapia , Animais , Transplante de Microbiota Fecal/métodos , Fezes/microbiologia , Lactobacillus/fisiologia , Masculino , Microbiota/fisiologia , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Several studies have found that bilingualism can delay the age of onset of Alz-heimer disease (AD). The interpretation of these findings is that switching between two languages can enhance cognitive reserve. However, some studies have provided inconsistent results. Diverse language pairs used by the bilinguals in different studies may contribute to the discrepancies. Cantonese and Mandarin are widely used in southern China, and regarded as bilingualism. The present study aims to determine if Cantonese/Mandarin bilingualism can delay the onset of AD. METHODS: The data of 129 patients diagnosed with probable AD, including 48 Cantonese monolinguals, 20 Mandarin monolinguals, and 61 Cantonese/Mandarin bilinguals were analyzed. RESULTS: Cantonese/Mandarin bilinguals were found to have an older age at AD onset, and older age at the first clinic visit than Mandarin monolinguals and Cantonese monolinguals. Both Mandarin monolinguals and Cantonese/Mandarin bilinguals had a higher education level and higher occupation status than the Cantonese monolinguals. Mandarin monolinguals did not differ from Cantonese/Mandarin bilinguals significantly in years of education and occupation status. The multiple linear regression analyses indicated that Cantonese/Mandarin bilingualism can delay the onset of AD independently. CONCLUSION: Constantly speaking both Cantonese and Mandarin from at least early adulthood can delay the onset of AD.
Assuntos
Doença de Alzheimer , Reserva Cognitiva , Multilinguismo , Idade de Início , Idoso , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/psicologia , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de ProteçãoRESUMO
OBJECTIVE: To evaluate the efficacy of soluble programmed death-1 (sPD-1) for risk stratification and prediction of 28-day mortality in patients with sepsis, we compared serum sPD-1 with procalcitonin (PCT), C-reactive protein (CRP), and the Mortality in Emergency Department Sepsis (MEDS) score. METHODS: A total of 60 healthy volunteers and 595 emergency department (ED) patients were recruited for this prospective cohort study. According to the severity of their condition on ED arrival, the patients were allocated to the systemic inflammatory response syndrome group (130 cases), sepsis group (276 cases), severe sepsis group (121 cases), and septic shock group (68 cases). In addition, all patients with sepsis were also divided into the survivor group (349 cases) and nonsurvivor group (116 cases) according to the 28-day outcomes. RESULTS: When the severity of sepsis increased, the levels of sPD-1 gradually increased. The levels of sPD-1, PCT, CRP and the MEDS score were also higher in the nonsurvivor group compared to the survivor group. Logistic regression suggested that sPD-1, PCT, and the MEDS score were independent risk factors for 28-day mortality of patients with sepsis. Area under the curve (AUC) of sPD-1, PCT and the MEDS score for 28-day mortality was 0.725, 0.693, and 0.767, respectively, and the AUC was improved when all 3 factors were combined (0.843). CONCLUSION: Serum sPD-1 is positively correlated with the severity of sepsis, and it is valuable for risk stratification of patients and prediction of 28-day mortality. Combining sPD-1 with PCT and the MEDS score improves the prognostic evaluation.
Assuntos
Calcitonina/sangue , Serviço Hospitalar de Emergência , Receptor de Morte Celular Programada 1/sangue , Sepse/mortalidade , Idoso , Área Sob a Curva , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , China , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROC , Medição de Risco , Fatores de Risco , Sepse/sangue , Índice de Gravidade de Doença , Fatores de TempoRESUMO
Sustained activation of NLRP3 inflammasome is closely related to diabetes and stroke. However, it is unknown whether NLRP3 inflammasome plays an essential role in stroke in diabetes. We aim to investigate the effect and the potential mechanism of NLRP3 inflammasome in diabetic mice with cerebral ischemia-reperfusion injury. A type 2 diabetic mouse model was induced by a high-fat diet and streptozotocin (STZ). Diabetic mice received MCC950 (the specific molecule NLRP3 inhibitor) or vehicle 60 minutes before the middle cerebral artery occlusion (MCAO) and reperfusion. MCC950 reduced the neurological deficit score of 24 h after cerebral ischemia reperfusion and improved the 28-day survival rate of cerebral ischemia-reperfusion injury in diabetic mice. Furthermore, we found that the mRNA transcription levels of NLRP3, IL-1ß, and caspase-1 in the core ischemic area were remarkably amplified in diabetic mice with cerebral ischemia-reperfusion injury, whereas this phenomenon was obviously attenuated by MCC950 pretreatment. In conclusion, the NLRP3 inflammasome was involved in the complex diseases of diabetic stroke. MCC950, the NLRP3 specific inhibitor, ameliorated diabetic mice with cerebral ischemia-reperfusion injury and improved the 28-day survival rate during the recovery stage of ischemic stroke.