RESUMEN
BACKGROUND: Extreme temperature events (ETEs), including heatwaves and cold spells, are attracting increasing attention because of their impacts on human health. However, the association between ETEs and cardiometabolic multimorbidity (CMM) and the role of functional dependency in this relationship remain unclear. METHODS: A prospective cohort study was conducted using data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2020, considering 12 definitions each for heatwaves and cold spells, and three levels of functional dependency. Mixed Cox models with time-varying variables were used to comprehensively assess the independent and combined effects of ETEs and functional dependency on CMM. Additionally, subgroup analyses were conducted to investigate whether the relationship between ETEs and CMM was modified by the baseline characteristics. RESULTS: Heatwave and cold spell exposures were associated with an increased risk of CMM (HR range: 1.028-1.102 and 1.046-1.187, respectively). Compared to participants with normal functional abilities, the risk of CMM increased with higher levels of functional dependency (HR range: 1.938-2.185). ETEs exposure and functional dependency are jointly associated with CMM risk. Participants with high-intensity ETEs exposure and high functional dependency had the greatest risk of developing CMM. Participants aged 60 and above were more susceptible to the effects of ETEs on CMM. Additionally, urban residents and those in northern regions were more vulnerable to heatwaves. CONCLUSION: Both ETEs exposure and functional dependency increase the risk of developing CMM. Participants with functional dependency exposed to high-intensity ETEs faced the highest risk of developing CMM. These findings highlight the significant impact of ETEs on CMM and the importance of protecting vulnerable populations during periods of extreme temperature.
RESUMEN
In multiple myeloma (MM), while frequent mutations in driver genes are crucial for disease progression, they traditionally offer limited insights into patient prognosis. This study aims to enhance prognostic understanding in MM by analyzing pathway dysregulations in key cancer driver genes, thereby identifying actionable gene signatures. We conducted a detailed quantification of mutations and pathway dysregulations in 10 frequently mutated cancer driver genes in MM to characterize their comprehensive mutational impacts on the whole transcriptome. This was followed by a systematic survival analysis to identify significant gene signatures with enhanced prognostic value. Our systematic analysis highlighted 2 significant signatures, TP53 and LRP1B, which notably outperformed mere mutation status in prognostic predictions. These gene signatures remained prognostically valuable even when accounting for clinical factors, including cytogenetic abnormalities, the International Staging System (ISS), and its revised version (R-ISS). The LRP1B signature effectively distinguished high-risk patients within low/intermediate-risk categories and correlated with significant changes in the tumor immune microenvironment. Additionally, the LRP1B signature showed a strong association with proteasome inhibitor pathways, notably predicting patient responses to bortezomib and the progression from monoclonal gammopathy of unknown significance to MM. Through a rigorous analysis, this study underscores the potential of specific gene signatures in revolutionizing the prognostic landscape of MM, providing novel clinical insights that could influence future translational oncology research.
RESUMEN
Background: Older age and female sex are risk factors for osteoarthritis and osteoporosis (OP). This study evaluated the knowledge, attitudes, and practices of patients with knee osteoarthritis (KOA) in China regarding OP and its prevention. This cross-sectional, questionnaire-based study enrolled patients with KOA at four grade-A tertiary hospitals in Shandong Province between 1st September and 20th November 2022. Methods: The administered questionnaire contained 55 items across four dimensions (demographic information, knowledge, attitude, and practice). Logistic regression analyses were performed to identify factors associated with an overall questionnaire score ≥70% of the maximum possible score. SPSS 26.0 was used for the analyses; P<0.05 was considered significant. Results: The analysis included 434 participants (261 females). The median knowledge, attitude, and practice scores were 7 (interquartile range: 5-10) (possible range, 0-17 points), 44 (interquartile range: 42-49) (possible range, 11-55 points), and 43 (interquartile range: 38-47) (possible range, 13-65 points), respectively. Multivariable logistic regression indicated that female sex (odds ratio [OR], 2.421; 95% confidence interval [95% CI] 1.558-3.762; P<0.001), age 56-65 years-old (OR, 4.222; 95% CI, 1.763-10.109; P=0.001 vs ≤55 years-old), age >65 years-old (OR, 4.358; 95% CI, 1.863-10.195; P=0.001 vs ≤55 years-old), middle/high/technical secondary school education (OR, 1.853; 95% CI, 1.002-3.428; P=0.049 vs primary school or below), and having KOA for 4-5 years (OR, 2.682; 95% CI, 1.412-5.094; P=0.003 vs ≤3 years) were independently associated with a high KAP score. Conclusion: There is room for improvement in the knowledge and practices of patients with osteoarthritis in China regarding OP. The findings of this study may facilitate the design and implementation of education programs to increase awareness about OP prevention among patients with KOA.
RESUMEN
[This retracts the article DOI: 10.3892/ol.2018.8110.].
RESUMEN
[This retracts the article DOI: 10.3892/ol.2018.9335.].
RESUMEN
Background: Randomized trials have shown a survival benefit for fruquintinib over placebo in patients with metastatic colorectal cancer (mCRC) that progressed after standard therapies, but real-world prognostic analyses have been seldom reported. We evaluated survival, safety outcomes, and predictive and prognostic factors in patients treated with fruquintinib in a real-life setting. Methods: We conducted a multi-center study by collecting relevant data on patients with advanced colorectal cancer (CRC) who received fruquintinib, focusing on progression-free survival (PFS), overall survival (OS), and L3 skeletal muscle index (SMI), including safety follow-up. Results: From January 2020 to January 2022, a total of 140 patients were selected and included in this study. The cut-off date was 30 July 2022. The median follow-up time was 18.3 months (range, 6-29.3 months) and the median age of included cases was 63 years (range, 32-81 years). The median PFS and OS for the 140 patients was 6.3 and 12.6 months, respectively. The median PFS and OS for the 76 patients who were included in SMI analysis was 6.0 and 12.0 months, respectively. Multivariate analysis suggested brain metastasis {hazard ratio (HR) [95% confidence interval (CI)]: 2.779 (1.162-6.646), P=0.02}, decrease in SMI of >5% [HR (95% CI): 9.732 (2.201-43.028), P=0.003], and baseline carcinoembryonic antigen (CEA) level [HR (95% CI): 4.061 (1.391-11.858), P=0.01] as independent predictors of OS. The most common treatment-related adverse events (TRAEs) were hypertension (24, 17.1%), fatigue (21, 15%), and hand-foot syndrome (20, 14.3%); 9 (13.6%) and 15 (10.7%) patients had dose reduction and treatment discontinuation due to TRAEs respectively. Conclusions: The real-world efficacy and safety of fruquintinib in advanced CRC patients are numerically superior to that in the previous phase III studies. SMI, brain metastasis and CEA could serve as potential markers for patient selection.
RESUMEN
Vascular endothelial inflammation is crucial in hepatic ischemia-reperfusion injury (IRI). Our previous research has shown that connective tissue growth factor (CTGF), secreted by endothelial cells, protects against acute liver injury, but its upstream mechanism is unclear. We aimed to clarify the protective role of CTGF in endothelial cell inflammation during IRI and reveal the regulation between endoplasmic reticulum stress-induced activating transcription factor 6 (ATF6) and CTGF. Hypoxia/reoxygenation in endothelial cells, hepatic IRI in mice and clinical specimens were used to examine the relationships between CTGF and inflammatory factors and determine how ATF6 regulates CTGF and reduces damage. We found that activating ATF6 promoted CTGF expression and reduced liver damage in hepatic IRI. In vitro, activated ATF6 upregulated CTGF and downregulated inflammation, while ATF6 inhibition had the opposite effect. Dual-luciferase assays and chromatin immunoprecipitation confirmed that activated ATF6 binds to the CTGF promoter, enhancing its expression. Activated ATF6 increases CTGF and reduces extracellular regulated protein kinase 1/2 (ERK1/2) phosphorylation, decreasing inflammatory factors. Conversely, inhibiting ATF6 decreases CTGF and increases the phosphorylation of ERK1/2, increasing inflammatory factor levels. ERK1/2 inhibition reverses this effect. Clinical samples have shown that CTGF increases after IRI, inversely correlating with inflammatory cytokines. Therefore, ATF6 activation during liver IRI enhances CTGF expression and reduces endothelial inflammation via ERK1/2 inhibition, providing a novel target for diagnosing and treating liver IRI.
RESUMEN
Metalo hydrogen-bonded organic frameworks (MHOFs) have received growing interest in designing crystalline functional materials. However, reports on bifunctional MHOFs showing magnetic and proton-conductive properties are extremely limited and their design is challenging. Herein, we investigated the magnetic and proton-conductive properties of two sulfonated CoHOF and MnHOF, {M(H2O)2(abs)2}n (M = Co2+ and Mn2+, Habs = 4-aminoazobenzene-4'-sulfonic anion), constructed by coordination chains. The supramolecular frameworks sustained by H bonds between -SO3- and coordinated water show directional ladder-type H bonds with hydrophilic nanochannels, leading to high proton conduction with exceptionally high conductivity around 10-2 S cm-1 at 100 °C under 97% relative humidity. In particular, the maximum σ value of CoHOF, 2.11 × 10-2 S cm-1, recorded the highest value among the reported proton-conducting materials showing slow magnetic relaxation. Meanwhile, the molecular structure of organosulfonate enables the magnetic isolation of high-spin Co2+ and Mn2+ centers in the frameworks. Magnetic measurements indicated that the MHOFs show field-induced single-ion magnet (SIM) properties, making these compounds rare magnetic-proton-conductive MHOFs. The work provides not only two unique MHOFs with SIM behavior and high proton conduction performance but also avenues for designing stable bifunctional MHOFs via a coordination chain approach.
RESUMEN
BACKGROUND: Thyroid hormone is the key endocrine regulator of growth, development, metabolism, and other bodily functions. α-Klotho has been involved in the aging process and acts as an endocrine factor involved in the regulation of various metabolic processes in humans. However, the relationship between α-Klotho and thyroid profile has not been uniformly recognize. OBJECTIVE: To determine the relationship between α-Klotho and thyroid profile in adult individuals. METHODS: Population data of 4614 adult individuals were obtained from the NHANES database during the period of 2007-2012. Weighted multivariable regression analysis was performed using a general linear model with serum α-Klotho as the independent variable and thyroid profile as the dependent variables, respectively. The generalized additive model was used for smoothing curve fitting and threshold effect analysis. RESULTS: α-Klotho was associated with a slightly higher FT3, TT3 and TT4 level in unadjusted and adjusted regression models. However, a higher α-Klotho level was associated with a lower TSH level. After α-Klotho was grouped as quantiles with reference (Q1), α-Klotho still showed a statistically significant positive correlation with FT3 and TT3 levels in Q2, Q3 and Q4. In addition, α-Klotho was positively corrected with TT4, but negatively associated with TSH in Q4. CONCLUSIONS: Serum soluble α-Klotho was positively associated with FT3, TT3 and TT4, but negatively correlated with TSH. The significant effect of α-Klotho on thyroid profile suggests its potential as a predictive marker of thyroid functions, indicating its possible involvement in the regulation of thyroid hormone secretion.
Asunto(s)
Proteínas Klotho , Encuestas Nutricionales , Glándula Tiroides , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Glándula Tiroides/metabolismo , Hormonas Tiroideas/sangre , Glucuronidasa/sangre , Biomarcadores/sangre , Pruebas de Función de la Tiroides , Estudios Transversales , Anciano , Adulto JovenRESUMEN
Small extracellular vesicles (sEVs) are important mediators of intercellular communication between tumor cells and their surrounding environment. Furthermore, the mechanisms by which miRNAs carried in tumor sEVs regulate macrophage polarization remain largely unknown. To concentrate sEVs, we used the traditional ultracentrifugation method. Western blot, NanoSight, and transmission electron microscopy were used to identify sEVs. To determine the function of sEVs-miR-487a, we conducted in vivo and in vitro investigations. The intercellular communication mechanism between osteosarcoma cells and M2 macrophages, mediated by sEVs carrying miR-487a, was validated using luciferase reporter assays, transwell assays, and Western blot analysis. In vitro, sEVs enriched in miR-487a and delivered miR-487a to macrophages, promoting macrophage polarization toward an M2-like type, which promotes proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of osteosarcoma cells. In vivo, sEVs enriched in miR-487a facilitate lung metastasis of osteosarcoma. Moreover, plasma miR-487a in sEVs was shown to be a potential biomarker applicable for osteosarcoma diagnosis. In summary, miR-487a derived from osteosarcoma cells can be transferred to macrophages via sEVs, then promote macrophage polarization towards an M2-like type by targeting Notch2 and activating the GATA3 pathway. In a feedback loop, the activation of macrophages accelerates epithelial-mesenchymal transition (EMT), which in turn promotes the migration, invasion, and lung metastasis of osteosarcoma cells. This reciprocal interaction between activated macrophages and osteosarcoma cells contributes to the progression of the disease. Our data demonstrate a new mechanism that osteosarcoma tumor cells derived exosomal-miR-487a which is involved in osteosarcoma development by regulating macrophage polarization in tumor microenvironment (TME).
RESUMEN
In the past few years, mass spectrometry imaging (MSI) has brought many new inspirations to plant research. However, current MSI experiments usually include only a single batch of samples, casting doubts on the reproducibility of phytochemical distribution across different batches. Consequently, MSI has seldom been applied to conduct species discrimination. In this experiment, MSI was employed to discriminate between two taxonomically similar plants, Scutellaria baicalensis Georgi and Scutellaria rehderiana Diels. A new concept termed a "spatial marker" was proposed in this article, which referred to the phytochemical marker that presented both intraspecies similarity and interspecies dissimilarity. Multiple batches of S. baicalensis and S. rehderiana were analyzed using MSI, proving that the authentication protocol using spatial markers was reliable and reproducible. The observed spatial markers were further identified using on-tissue tandem mass spectrometry and liquid chromatography coupled with mass spectrometry. Additionally, the spectral data collected from MSI were utilized to set up algorithm models for species discrimination. External validation confirmed that the established random forest model was extrapolated well to unknown samples. Overall, this investigation successfully explored the analytical applicability of MSI, facilitating rapid authentication of medicinal plants.
Asunto(s)
Plantas Medicinales , Scutellaria baicalensis , Plantas Medicinales/química , Plantas Medicinales/clasificación , Scutellaria baicalensis/química , Espectrometría de Masas en Tándem/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Especificidad de la Especie , Reproducibilidad de los Resultados , Espectrometría de Masas/métodos , AlgoritmosRESUMEN
Our study examines the causal effect of rural hospital closures on nearby hospitals' nurse staffing levels and health care utilization. We use data from the 2014-2019 American Hospital Association Survey on nurse staffing level outcomes including licensed practical or vocational nurses (LPNs), registered nurses (RNs), and advanced practice nurses (APNs); and health care utilization outcomes, including inpatient and outpatient surgical operations and emergency department (ED) visits. Using propensity score matching and difference-in-differences (DID) methods, we find that rural hospital closures lead to an average increase of 37.3% in the number of nurses in nearby rural hospitals during the 4 years following the closure. This increase is found across all categories of nurses, including LPNs, RNs, and APNs. We also find a substantial increase in the provision of inpatient and outpatient surgical operations but there is no change in ED visits. We do not find any effects for nearby urban hospitals. Our study suggests that a large proportion of the nursing workforce relocates to nearby hospitals after a rural hospital closure, which mitigates the negative consequences of such closures and allows these nearby hospitals to provide a larger volume of highly profitable services.
RESUMEN
Previous findings have indicated the potential benefits of the Chinese traditional medicine Qiliqiangxin (QLQX) in heart failure. Here we performed a double-blind, randomized controlled trial to evaluate the efficacy and safety of QLQX in patients with heart failure and reduced ejection fraction (HFrEF). This multicenter trial, conducted in 133 hospitals in China, enrolled 3,110 patients with HFrEF with NT-proBNP levels of ≥450 pg ml-1 and left ventricular ejection fraction of ≤40%. Participants were randomized to receive either QLQX capsules or placebo (four capsules three times daily) alongside standard heart failure therapy. The trial met its primary outcome, which was a composite of hospitalization for heart failure and cardiovascular death: over a median follow-up of 18.3 months, the primary outcome occurred in 389 patients (25.02%) in the QLQX group and 467 patients (30.03%) in the placebo group (hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.68-0.90; P < 0.001). In an analysis of secondary outcomes, the QLQX group showed reductions in both hospitalization for heart failure (15.63% versus 19.16%; HR, 0.76; 95% CI, 0.64-0.90; P = 0.002) and cardiovascular death (13.31% versus 15.95%; HR, 0.83; 95% CI, 0.68-0.996; P = 0.045) compared to the placebo group. All-cause mortality did not differ significantly between the two groups (HR, 0.84; 95% CI, 0.70-1.01; P = 0.058) and adverse events were also comparable between the groups. The results of this trial indicate that QLQX may improve clinical outcomes in patients with HFrEF when added to conventional therapy. ChiCTR registration: ChiCTR1900021929 .
Asunto(s)
Medicamentos Herbarios Chinos , Insuficiencia Cardíaca , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/efectos adversos , Medicamentos Herbarios Chinos/administración & dosificación , Masculino , Femenino , Método Doble Ciego , Volumen Sistólico/efectos de los fármacos , Persona de Mediana Edad , Anciano , Medicina Tradicional China , Resultado del Tratamiento , Hospitalización , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangreRESUMEN
IL-26 is a crucial inflammatory cytokine that participates in defending host cells against infections. We initially cloned and identified the cDNA sequences of interleukin (IL)-26 in channel catfish (Ictalurus punctatus). The open reading frame (ORF) of IpIL-26 was 537 bp in length, encoding 178 amino acids (aa). Constitutive expression of IpIL-26 was observed in tested tissues, with the highest level found in the gill and spleen. To explore the function of IpIL-26 in channel catfish, different stimuli were used to act on both channel catfish and channel catfish kidney cells (CCK). The expression of IpIL-26 could be up-regulated by bacteria and viruses in multiple tissues. In vitro, recombinant IpIL-26 (rIpIL-26) could induce the expression levels of inflammatory cytokines such as TNF-α, IL-1ß, IL-6, IL-20, and IL-22 playing vital roles in defending the host against infections. Our results demonstrated that IpIL-26 might be an essential cytokine, significantly affecting the immune defense of channel catfish against pathogen infections.
Asunto(s)
Secuencia de Aminoácidos , Enfermedades de los Peces , Proteínas de Peces , Regulación de la Expresión Génica , Ictaluridae , Inmunidad Innata , Interleucinas , Filogenia , Alineación de Secuencia , Animales , Ictaluridae/inmunología , Ictaluridae/genética , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Proteínas de Peces/química , Interleucinas/genética , Interleucinas/inmunología , Inmunidad Innata/genética , Enfermedades de los Peces/inmunología , Alineación de Secuencia/veterinaria , Regulación de la Expresión Génica/inmunología , Perfilación de la Expresión Génica/veterinaria , Secuencia de Bases , ADN Complementario/genéticaRESUMEN
BACKGROUND: Acute ischemic stroke presents significant challenges in healthcare, notably due to the risk and poor prognosis associated with hemorrhagic transformation (HT). Currently, there is a notable gap in the early clinical stage for a valid and reliable predictive model for HT. METHODS: This single-center retrospective study analyzed data from 224 patients with acute ischemic stroke due to large vessel occlusion. We collected comprehensive clinical data, CT, and CTP parameters. A predictive model for HT was developed, incorporating clinical indicators alongside imaging data, and its efficacy was evaluated using decision curve analysis and calibration curves. In addition, we have also built a free browser-based online calculator based on this model for HT prediction. RESULTS: The study identified atrial fibrillation and hypertension as significant risk factors for HT. Patients with HT showed more extensive initial ischemic damage and a smaller ischemic penumbra. Our novel predictive model, integrating clinical indicators with CT and CTP parameters, demonstrated superior predictive value compared to models based solely on clinical indicators. CONCLUSIONS: The research highlighted the intricate interplay of clinical and imaging parameters in HT post-thrombectomy. It established a multifaceted predictive model, enhancing the understanding and management of acute ischemic stroke. Future studies should focus on validating this model in broader cohorts, further investigating the causal relationships, and exploring the nuanced effects of these parameters on patient outcomes post-stroke.
Asunto(s)
Accidente Cerebrovascular Isquémico , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Persona de Mediana Edad , Factores de Riesgo , Valor Predictivo de las Pruebas , Pronóstico , Anciano de 80 o más Años , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/etiología , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico por imagen , TrombectomíaRESUMEN
Over the past century, environmental changes have significantly impacted wheat spike morphology, crucial for adaptation and grain yield. However, the changes in wheat spike modifications during this period remain largely unknown. This study examines 16 spike morphology traits in 830 accessions released from 1900 to 2020. It finds that spike weight, grain number per spike (GN), and thousand kernel weight have significantly increased, while spike length has no significant change. The increase in fertile spikelets is due to fewer degenerated spikelets, resulting in a higher GN. Genome-wide association studies identified 49,994 significant SNPs, grouped into 293 genomic regions. The accumulation of favorable alleles in these genomic regions indicates the genetic basis for modification in spike morphology traits. Genetic network analysis of these genomic regions reveals the genetic basis for phenotypic correlations among spike morphology traits. The haplotypes of the identified genomic regions display obvious geographical differentiation in global accessions and environmental adaptation over the past 120 years. In summary, we reveal the genetic basis of adaptive evolution and the interactions of spike morphology, offering valuable resources for the genetic improvement of spike morphology to enhance environmental adaptation.
RESUMEN
Background: Postmenopausal osteoporosis (PMOP) increases fracture risk in women. Though traditional treatments are slow to act, combining romosozumab with conventional therapy shows promise. Despite its growing use, studies on effectiveness are limited. This study aims to systematically evaluate the combined therapy's impact on pain relief, disease progression, and adverse reactions in PMOP patients. Methods: Databases including PubMed, EMBASE, ScienceDirect, and the Cochrane Library were searched from their inception to September 2023 to identify randomized controlled trials (RCTs) evaluating the role of romosozumab in PMOP. Random or fixed effect models were employed for statistical analysis. Two reviewers independently assessed the quality of the included studies and extracted the data. The meta-analysis was conducted using RevMan 5.4 software. Results: Six RCTs with a total sample size of 17,985 cases were included. The incidence of vertebral fractures was compared and analyzed after 12 and 24 months of treatment. Romosozumab significantly reduced the incidence of vertebral fractures at 24 months (OR = 0.36; 95% CI: 0.35-0.52) but not at 12 months (OR = 0.39; 95% CI: 0.14-1.05). It was also associated with a decreased incidence of nonvertebral fractures (OR = 0.79; 95% CI: 0.66-0.94) and clinical fractures at 24 months (OR = 0.70; 95% CI: 0.59-0.82) compared to standard therapy. Romosozumab demonstrated a significant improvement in percentage change in bone mineral density (BMD) [mean difference (MD) = 10.38; 95% CI: 4.62-16.14] and in hip joint BMD (MD = 4.24; 95% CI: 2.92-5.56). There was no notable difference in adverse reactions compared to standard care (p > 0.05). Funnel plots displayed a predominantly symmetrical pattern, suggesting no evidence of publication bias in the selected literature. Conclusion: Combining romosozumab with conventional therapy effectively treats PMOP, significantly reducing vertebral, non-vertebral, and clinical fractures while increasing BMD in the hip, femoral neck, and lumbar spine. However, further high-quality studies are needed for validation.
RESUMEN
End-ischemic normothermic mechanical perfusion (NMP) could provide a curative treatment to reduce cholestatic liver injury from donation after circulatory death (DCD) in donors. However, the underlying mechanism remains elusive. Our previous study demonstrated that air-ventilated NMP could improve functional recovery of DCD in a preclinical NMP rat model. Here, metabolomics analysis revealed that air-ventilated NMP alleviated DCD- and cold preservation-induced cholestatic liver injury, as shown by the elevated release of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and γ-glutamyl transferase (GGT) in the perfusate (p < .05) and the reduction in the levels of bile acid metabolites, including ω-muricholic acid, glycohyodeoxycholic acid, glycocholic acid, and glycochenodeoxycholate (GCDC) in the perfused livers (p < .05). In addition, the expression of the key bile acid metabolism enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1), which is predominantly expressed in hepatocytes, was substantially elevated in the DCD rat liver, followed by air-ventilated NMP (p < .05), and in vitro, this increase was induced by decreased GCDC and hypoxia-reoxygenation in the hepatic cells HepG2 and L02 (p < .05). Knockdown of UGT1A1 in hepatic cells by siRNA aggravated hepatic injury caused by GCDC and hypoxia-reoxygenation, as indicated by the ALT and AST levels in the supernatant. Mechanistically, UGT1A1 is transcriptionally regulated by peroxisome proliferator-activator receptor-γ (PPAR-γ) under hypoxia-physoxia. Taken together, our data revealed that air-ventilated NMP could alleviate DCD- and cold preservation-induced cholestatic liver injury through PPAR-γ/UGT1A1 axis. Based on the results from this study, air-ventilated NMP confers a promising approach for predicting and alleviating cholestatic liver injury through PPAR-γ/UGT1A1 axis.
Asunto(s)
PPAR gamma , Animales , Ratas , PPAR gamma/metabolismo , PPAR gamma/genética , Masculino , Humanos , Glucuronosiltransferasa/metabolismo , Glucuronosiltransferasa/genética , Hígado/metabolismo , Hígado/patología , Colestasis/metabolismo , Perfusión , Ratas Sprague-Dawley , Preservación de Órganos/métodos , Trasplante de HígadoRESUMEN
Nocardia is an anthropozoonotic bacteria that occurs widely in the natural environment. However, because it is a gram-positive aerobic opportunistic pathogen, it rarely occurs in patients with no prior history of immune function disease. Since the symptoms are nonspecific the diagnosis of Nocardia pneumonia is challenging. Previous studies have not reported that this anthropozoonotic bacteria colonizing the human body could cause severe pneumonia by gingival pain and pharyngeal discomfort. This case report describes a previously healthy 60-year-old female farmer who presented to the doctor with gingival pain and pharyngeal discomfort. She was treated with a dental cleaning and oral metronidazole. The patient rapidly progressed to breathing difficulties. Lung shadow was found by computerized tomography examination. The radiologist diagnosed pulmonary tuberculosis as image-based. Through laboratory examination and culture of pathogenic microorganisms in the sputum and blood of the patient, no obvious positive findings were found. The disease progressed rapidly to tracheal intubation ventilator assisted breathing. Subsequently, the patient underwent alveolar lavatory examination under endotracheal intubation fiberbronchoscopy, and the culture of alveolar lavage fluid indicated Nocardia. According to this result, the patient's disease was quickly controlled after selecting the targeted drug compound sulfamethoxazole and intravenous meropenem for treatment. In view of the reason for the high misdiagnosis rate due to the low positive rate of Nocardia culture in most cases, the clinical thinking of diagnosis and treatment from oral infection symptoms to fatal pneumonia reported in this case has certain clinical popularization and enlighten significance, not only improved the diagnosis and treatment of rare diseases, but also be reduced medical disputes.
RESUMEN
Background: Cancer and psychiatric symptoms are associated. Fear of cancer recurrence (FCR) is the most common psychological problem for cancer survivors. Pharmacological interventions can help, but also have major drawbacks. Music therapy and music interventions have been shown to be a safe and practical complementary treatment. Objective: This randomized, controlled trial aimed to investigate the effects of music therapy and music intervention in attenuating non-small cell lung cancer (NSCLC) patients' anxiety related to FCR. Methods: NSCLC patients with FCR were randomly allocated to a music therapy and intervention group (G1) and Control group (G2). Patients' anxiety was measured using the State-Trait Anxiety Inventory scores and heart rates. Primary outcome measure were PET scans. Secondary measures were salivary cortisol, salivary α-amylase levels and heart rate. Findings: Patients in G1 showed higher glucose metabolism of 18F-FDG in the superior frontal gyrus, anterior cingulate, superior temporal gyrus, and parahippocampal gyrus, compared to those in G2 (all P < .001). Heart rates and salivary α-amylase area under the curve (AUC) and relative variation (VAR) in G1 were significantly lower than those in G2 (all P < .05). State-Trait Anxiety Inventory scores and cortisol AUC in G1 were significantly lower than those in G2 (all P < .05). Conclusions: Music therapy and interventions can reduce anxiety and endocrinological responses and change glucose metabolism of 18F-FDG in fear-related brain regions.Trial registration: Registered retrospectively, ISRCTN Registry, www.isrctn.com, ISRCTN23276302Clinical Implications: Cancer treatment centers and physical examination centers should consider providing music therapy and intervention to the appropriate patients as a routine component of a comprehensive clinical care during medical examinations.