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BACKGROUND: Given the previously reported harmful effects of abdominal fat burden on kidney function, we aim to investigate the relationship between major adverse kidney events within 30 days (MAKE30) and abdominal obesity in acute necrotizing pancreatitis (ANP) patients and explore the underlying risk factors. METHODS: A retrospective cohort study of all patients admitted within 72 h after the first episode of ANP to a tertiary center between June 2015 and June 2019 was conducted. Automatic image analysis software was used to calculate the area of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and skeletal muscle from computed tomography scans at the umbilical level. The potential risk factors of MAKE30 were analyzed by logistic regression. RESULTS: A total of 208 eligible ANP patients were enrolled, with an incidence of 23% for MAKE30. VAT area was more closely associated with the development of MAKE30, with an area under the ROC curve of 0.69 (cutoff value 200 cm2, 63.8% sensitivity and 66.7% specificity). Multivariate logistic regression analysis demonstrated that VAT area [OR 1.01 (1.01-1.02); p < 0.001] was an independent risk factor in predicting MAKE30. Patients with a VAT area > 200 cm2 had more requirements of renal replacement therapy (32% vs. 12%, P < 0.001), and a significantly higher incidence of other poor clinical outcomes (all p < 0.05). CONCLUSION: Early assessment of the VAT area may help identify ANP patients at high risk of MAKE30, suggesting that it could be a potential indicator for adverse kidney events.
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BACKGROUND: A stent with characteristics of a hybrid design may have advantages in improving the patency of symptomatic iliofemoral vein obstruction. This study assessed the safety and effectiveness of the V-Mixtent Venous Stent in treating symptomatic iliofemoral outflow obstruction. METHODS: Eligible patients had a Clinical-Etiologic-Anatomic-Physiologic (CEAP) C classification of ≥ 3 or a Venous Clinical Severity Score (VCSS) pain score of ≥ 2. The primary safety endpoint was the rate of major adverse events within 30 days. The primary effectiveness endpoint was the 12-month primary patency rate. Secondary endpoints included changes in VCSS from baseline to 6 and 12 months, alterations in CEAP C classification, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) scores at 12 months, and stent durability measures. RESULTS: Between December 2020 and November 2021, 171 patients were enrolled across 15 institutions. A total of 185 endovenous stents were placed, with 91.81% of subjects receiving one stent and 8.19% receiving 2 stents. Within 30 days, only two major adverse events occurred (1.17%; 95% confidence interval [CI], 0.14-4.16%), below the literature-defined performance goal of 11% (P < .001). The 12-month primary patency rate (91.36%; 95% CI, 85.93-95.19%; P < .001) exceeded the literature-defined performance goal. VCSS changes from baseline demonstrated clinical improvement at 6 months (- 4.30 ± 3.66) and 12 months (- 4.98 ± 3.67) (P < .001). Significant reduction in symptoms, as measured by CEAP C classification and CIVIQ-14, was observed from pre-procedure to 12 months (P < .001). CONCLUSIONS: The 12-month outcomes confirm the safety and effectiveness of the V-Mixtent Venous Stent in managing symptomatic iliofemoral venous outflow obstruction, including clinical symptom improvement compared to before treatment.
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Vena Femoral , Vena Ilíaca , Stents , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Vena Femoral/cirugía , Vena Ilíaca/cirugía , Resultado del Tratamiento , Adulto , Anciano , Calidad de VidaRESUMEN
BACKGROUND: Non-small cell lung cancer (NSCLC) has a poor prognosis. Transvascular intervention is an important approach for treating NSCLC. Drug-eluting bead bronchial artery chemoembolisation (DEB-BACE) is a technique of using DEBs loaded with chemotherapeutic drugs for BACE. This study aims to conduct a meta-analysis to comprehensively assess the effectiveness and safety of DEB-BACE in treating NSCLC and investigate a novel therapeutic strategy for NSCLC. METHODS AND ANALYSIS: Wanfang, China National Knowledge Infrastructure, Medline (via PubMed), Cochrane Library, Scopus and Embase databases will be searched in November 2024. A meta-analysis will be conducted to assess the effectiveness and safety of DEB-BACE in the treatment of NSCLC. The following keywords will be applied: "Carcinoma, Non-Small-Cell Lung", "Non-Small Cell Lung Cancer", "Drug-Eluting Bead Bronchial Arterial Chemoembolization" and "drug-eluting beads". Reports in Chinese or English comparing the efficacy of DEB-BACE with other NSCLC treatment options will be included. Case reports, single-arm studies, conference papers, abstracts without full text and reports published in languages other than English and Chinese will not be considered. The Cochrane Handbook for Systematic Reviews of Interventions will be used to independently assess the risk of bias for each included study. In case of significant heterogeneity between studies, possible sources of heterogeneity will be explored through subgroup and sensitivity analysis. For the statistical analysis of the data, RevMan V.5.3 will be used. ETHICS AND DISSEMINATION: This meta-analysis will seek publication in a peer-reviewed journal on completion. Ethical approval is not required for this study as it is a database-based study. PROSPERO REGISTRATION NUMBER: CRD42023411392.
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Arterias Bronquiales , Carcinoma de Pulmón de Células no Pequeñas , Quimioembolización Terapéutica , Neoplasias Pulmonares , Metaanálisis como Asunto , Humanos , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Quimioembolización Terapéutica/métodos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamiento farmacológico , Proyectos de InvestigaciónRESUMEN
OBJECTIVE: To compare the effect of balanced multielectrolyte solutions(BMES) versus normal saline(NS) for intravenous fluid on chloride levels and clinical outcomes.in patients with predicted severe acute pancreatitis (pSAP). SUMMARY BACKGROUND DATA: Isotonic crystalloids are recommended for initial fluid therapy in acute pancreatitis, but whether the use of BMES in preference to NS confers clinical benefits is unknown. METHODS: In this multicenter, stepped-wedge, cluster-randomized trial, we enrolled patients with pSAP (APACHE II score ≥8 and C-reactive protein >150 mg/L) admitted within 72 hours of the advent of symptoms. The study sites were randomly assigned to staggered start dates for one-way crossover from the NS phase (NS for intravenous fluid) to the BMES phase(Sterofudin for intravenous fluid). The primary endpoint was the serum chloride concentration on trial day3. Secondary endpoints included a composite of clinical and laboratory measures. RESULTS: Overall, 259 patients were enrolled from eleven sites to receive NS(n=147) or BMES(n=112). On trial day3, the mean chloride level was significantly lower in patients who received BMES(101.8 mmol/L(SD4.8) versus 105.8 mmol/L(SD5.9), difference -4.3 mmol/L [95%CI -5.6 to -3.0 mmol/L];P<0.001). For secondary endpoints, patients who received BMES had less systemic inflammatory response syndrome(19/112,17.0% versus 43/147,29.3%, P=0.024) and increased organ failure-free days (3.9 d(SD2.7) versus 3.5days(SD2.7), P<0.001) by trial day7. They also spent more time alive and out of ICU(26.4 d(SD5.2) versus 25.0days(SD6.4), P=0.009) and hospital(19.8 d(SD6.1) versus16.3days(SD7.2), P<0.001) by trial day30. CONCLUSIONS: Among patients with pSAP, using BMES in preference to NS resulted in a significantly more physiological serum chloride level, which was associated with multiple clinical benefits(Trial registration number: ChiCTR2100044432).
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Aquaculture pond sediments have a notable influence on the ecosystem balance and farmed animal health. In this study, microalgal-bacterial immobilization (MBI) was designed to improve aquaculture pond sediments via synergistic interactions. The physicochemical characteristics, bacterial communities, and the removal efficiencies of emerging pollutants were systematically investigated. The consortium containing diatom Navicula seminulum and Alcaligenes faecalis was cultivated and established in the free and immobilized forms for evaluating the treatment performance. The results indicated that the immobilized group exhibited superior performance in controlling nutrient pollutants, shaping and optimizing the bacterial community compositions with the enrichment of functional bacteria. Additionally, it showed a stronger positive correlation between the bacterial community shifts and nutrient pollutants removal compared to free cells. Furthermore, the immobilized system maintained the higher removal performance of emerging pollutants (heavy metals, antibiotics, and pathogenic Vibrios) than free group. These findings confirmed that the employment of immobilized N. seminulum and A. faecalis produced more synergistic benefits and exerted more improvements than free cells in ameliorating aquaculture pond sediments, suggesting the potential for engineering application of functional microalgal-bacterial consortium in aquaculture.
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Acuicultura , Microalgas , Estanques , Microalgas/metabolismo , Sedimentos Geológicos/microbiología , Metales Pesados , Contaminantes Químicos del Agua/metabolismo , Bacterias/metabolismo , AnimalesRESUMEN
Human extrachromosomal circular DNA, or eccDNA, has been the topic of extensive investigation in the last decade due to its prominent regulatory role in the development of disorders including cancer. With the rapid advancement of experimental, sequencing and computational technology, millions of eccDNA records are now accessible. Unfortunately, the literature and databases only provide snippets of this information, preventing us from fully understanding eccDNAs. Researchers frequently struggle with the process of selecting algorithms and tools to examine eccDNAs of interest. To explain the underlying formation mechanisms of the five basic classes of eccDNAs, we categorized their characteristics and functions and summarized eight biogenesis theories. Most significantly, we created a clear procedure to help in the selection of suitable techniques and tools and thoroughly examined the most recent experimental and bioinformatics methodologies and data resources for identifying, measuring and analyzing eccDNA sequences. In conclusion, we highlighted the current obstacles and prospective paths for eccDNA research, specifically discussing their probable uses in molecular diagnostics and clinical prediction, with an emphasis on the potential contribution of novel computational strategies.
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OBJECTIVES: The study aimed to evaluate a simplified and practical frailty detection tool derived from the Fried frailty phenotype (FFP). This tool was developed to facilitate the identification of frail individuals in constrained settings, addressing the challenges posed by uncertain cutoffs of FFP indicators in prompt frailty assessment. DESIGN: A longitudinal study and a cross-sectional study. SETTINGS AND PARTICIPANTS: A total of 1978 older adults aged 67.4 ± 6.16 years from the China Health and Retirement Longitudinal Study (CHARLS), and 972 older adults aged 72.8 ± 6.75 years from a pilot cross-sectional study conducted in Shanghai communities. METHODS: Frailty was assessed according to the FFP criterion. A Chinese modified frailty phenotype (CMFP) was developed, incorporating specific cutoffs for grip strength and an alternative test for walk speed. The internal consistency reliability, the criterion, and predictive validity of the CMFP were evaluated. RESULTS: The 5-time chair stand test (5t-CST) was significantly associated with the 2.5-m walk test (r = 0.373 in the CHARLS and 0.423 in the pilot study). Each element of the CMFP showed moderate to strong correlations with the total CMFP score and showed Cronbach's alpha of 0.303 and 0.358 in both populations. The Spearman's r and kappa values between the CMFP and the FFP were 0.795 and 0.663 in the CHARLS, and 0.676 and 0.537 in the pilot study. The areas under the curve (AUC) were 0.936 and 0.928 in the 2 studies, respectively. In addition, frailty assessed by the CMFP significantly predicted future incidence of outcomes, including all-cause mortality, activities of daily living (ADL)/instrumental ADL disability, hospitalization, and depression. CONCLUSIONS AND IMPLICATIONS: The study demonstrated the CMFP as a valid tool, particularly highlighting its excellent predictive ability on outcomes. The 5t-CST may act as a viable alternative test for assessing slowness. The CMFP can be systematically integrated into preclinical practice to identify frail individuals, especially within constrained spaces.
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Anciano Frágil , Fragilidad , Evaluación Geriátrica , Fenotipo , Anciano , Femenino , Humanos , Masculino , China , Estudios Transversales , Pueblos del Este de Asia , Fragilidad/diagnóstico , Evaluación Geriátrica/métodos , Estudios Longitudinales , Proyectos Piloto , Reproducibilidad de los Resultados , Persona de Mediana EdadRESUMEN
Magnetic Induction Tomography (MIT) is a non-invasive imaging technique used for dynamic monitoring and early screening of cerebral hemorrhage. Currently, there is a significant challenge in cerebral hemorrhage MIT due to weak detection signals, which seriously affects the accuracy of the detection results. To address this issue, a dual-plane enhanced coil was proposed by combining the target field method with consideration of the spatial magnetic field attenuation pattern within the imaging target region. Simulated detection models were constructed using the proposed coil and cylindrical coil as excitation coils, respectively, and simulation imaging tests were conducted using the detection results. The simulation results indicate that compared to the cylindrical coil, the proposed coil enhances the linearity of the magnetic field within the imaging target region by 60.43%. Additionally, it effectively enhances the detection voltage and phase values. The simulation results of hemorrhage detection show that the proposed coil improves the accuracy of hemorrhage detection by 18.26%. It provides more precise detection results, offering a more reliable solution for cerebral hemorrhage localization and detection.
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Hemorragia Cerebral , Hemorragia Cerebral/diagnóstico por imagen , Humanos , Tomografía , Simulación por ComputadorRESUMEN
PURPOSE: The main objective is to quantify the lens nuclear opacity using spectral-domain optical coherence tomography (SD-OCT) and to evaluate its association with Lens Opacities Classification System III (LOCS-III) system, lens thickness (LT), and surgical parameters. The secondary objective is to assess the diagnostic model performance for hard nuclear cataract. METHODS: This study included 70 eyes of 57 adults with cataract, with 49 (70%) and 21 (30%) in training and validation cohort, respectively. Correlations of the average nuclear density (AND) /maximum nuclear density (MND) with LOCS-III scores, LT, and surgical parameters were analyzed. Univariate and multivariate logistic regression analysis, receiver operating characteristic curves and calibration curves were performed for the diagnostic of hard nuclear cataract. RESULTS: The pre-operative uncorrected distance visual acuity (UDVA), intraocular pressure (IOP), mean axial length (AL), and LT were 1.20 ± 0.47 log MAR, 15.50 ± 2.87 mmHg, 27.34 ± 3.77 mm and 4.32 ± 0.45 mm, respectively. The average nuclear opalescence (NO) and nuclear colour (NC) scores were 3.61 ± 0.94 and 3.50 ± 0.91 (ranging from 1.00 to 6.90), respectively. The average AND and MND were 137.94 ± 17.01 and 230.01 ± 8.91, respectively. NC and NO scores both significantly correlated with the AND (rNC = 0.733, p = 0.000; rNO = 0.755, p = 0.000) and MND (rNC = 0.643, p = 0.000; rNO = 0.634, p = 0.000). In the training cohort, the area under the curve (AUC) of the model was 0.769 (P < 0.001, 95%CI 0.620-0.919), which had a good degree of differentiation (Fig. 2a). The calibration curve showed good agreement between predicted and actual probability. CONCLUSION: The nuclear density measurement on SD-OCT images can serve as an objective and reliable indicator for quantifying nuclear density.
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Catarata , Núcleo del Cristalino , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Femenino , Masculino , Tomografía de Coherencia Óptica/métodos , Catarata/diagnóstico , Anciano , Persona de Mediana Edad , Núcleo del Cristalino/patología , Núcleo del Cristalino/diagnóstico por imagen , Agudeza Visual/fisiología , Curva ROC , Estudios Retrospectivos , Facoemulsificación , Anciano de 80 o más Años , Adulto , Cristalino/diagnóstico por imagen , Cristalino/patologíaRESUMEN
Deep learning models struggle to effectively capture data features and make accurate predictions because of the strong non-linear characteristics of arbitrage data. Therefore, to fully exploit the model performance, researchers have focused on network structure and hyperparameter selection using various swarm intelligence algorithms for optimization. Sparrow Search Algorithm (SSA), a classic heuristic method that simulates the sparrows' foraging and anti-predatory behavior, has demonstrated excellent performance in various optimization problems. Hence, in this study, the Multi-Strategy Modified Sparrow Search Algorithm (MSMSSA) is applied to the Long Short-Term Memory (LSTM) network to construct an arbitrage spread prediction model (MSMSSA-LSTM). In the modified algorithm, the good point set theory, the proportion-adaptive strategy, and the improved location update method are introduced to further enhance the spatial exploration capability of the sparrow. The proposed model was evaluated using the real spread data of rebar and hot coil futures in the Chinese futures market. The obtained results showed that the mean absolute percentage error, root mean square error, and mean absolute error of the proposed model had decreased by a maximum of 58.5%, 65.2%, and 67.6% compared to several classical models. The model has high accuracy in predicting arbitrage spreads, which can provide some reference for investors.
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Algoritmos , Gorriones , Gorriones/fisiología , Animales , Aprendizaje Profundo , Modelos TeóricosRESUMEN
Obesity-related hypertension (OH) is accompanied by obvious endothelial dysfunction, which contributes to increased peripheral vascular resistance and hypertension. Adrenomedullin (ADM), a multifunctional active peptide, is elevated in obese humans. The OH rats induced by high fat diet (HFD) for 28 weeks and the human umbilical vein endothelial cells (HUVECs)-treated by palmitic acid (PA) were used to investigate the effects of ADM on endothelial dysfunction and the underlying mechanisms. Vascular reactivity was assessed using mesenteric arteriole rings, and the protein expression levels were examined by Western blot analysis. Compared with the control rats, OH rats exhibited hypertension and endothelial dysfunction, along with reduced eNOS protein expression and Akt activation, and increased protein expression of proinflammatory cytokines and ROS levels. Four-week ADM administration improved hypertension and endothelial function, increased eNOS protein expression and Akt activation, and attenuated endothelial inflammation and oxidative stress in OH rats. In vitro experiment, the antagonism of ADM receptors with ADM22-52 and the suppression of Akt signaling with A6730 significantly blocked ADM-caused increase of NO content and activation of eNOS and Akt, and inhibited the anti-inflammatory and anti-oxidant effect of ADM in PA-stimulated HUVECs. These data indicate that endothelial dysfunction in OH rats is partially attributable to the decreased NO level, and the increased inflammation and oxidative stress. ADM improves endothelial function and exerts hypotensive effect depending on the increase of NO, and its anti-inflammatory and anti-oxidant effect via receptor-Akt pathway.
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Adrenomedulina , Endotelio Vascular , Células Endoteliales de la Vena Umbilical Humana , Hipertensión , Óxido Nítrico Sintasa de Tipo III , Obesidad , Proteínas Proto-Oncogénicas c-akt , Ratas Sprague-Dawley , Transducción de Señal , Animales , Adrenomedulina/farmacología , Adrenomedulina/metabolismo , Masculino , Obesidad/complicaciones , Obesidad/metabolismo , Hipertensión/metabolismo , Hipertensión/fisiopatología , Ratas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Humanos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Endotelio Vascular/metabolismo , Transducción de Señal/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo III/metabolismo , Dieta Alta en Grasa/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Receptores de Adrenomedulina/metabolismo , Fragmentos de PéptidosRESUMEN
AIMS: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients. METHODS: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. RESULTS: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally. CONCLUSION: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.
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BACKGROUND: Severe burns may alter the stability of the intestinal flora and affect the patient's recovery process. Understanding the characteristics of the gut microbiota in the acute phase of burns and their association with phenotype can help to accurately assess the progression of the disease and identify potential microbiota markers. METHODS: We established mouse models of partial thickness deep III degree burns and collected faecal samples for 16 S rRNA amplification and high throughput sequencing at two time points in the acute phase for independent bioinformatic analysis. RESULTS: We analysed the sequencing results using alpha diversity, beta diversity and machine learning methods. At both time points, 4 and 6 h after burning, the Firmicutes phylum content decreased and the content of the Bacteroidetes phylum content increased, showing a significant decrease in the Firmicutes/Bacteroidetes ratio compared to the control group. Nine bacterial genera changed significantly during the acute phase and occupied the top six positions in the Random Forest significance ranking. Clustering results also clearly showed that there was a clear boundary between the communities of burned and control mice. Functional analyses showed that during the acute phase of burn, gut bacteria increased lipoic acid metabolism, seleno-compound metabolism, TCA cycling, and carbon fixation, while decreasing galactose metabolism and triglyceride metabolism. Based on the abundance characteristics of the six significantly different bacterial genera, both the XGboost and Random Forest models were able to discriminate between the burn and control groups with 100% accuracy, while both the Random Forest and Support Vector Machine models were able to classify samples from the 4-hour and 6-hour burn groups with 86.7% accuracy. CONCLUSIONS: Our study shows an increase in gut microbiota diversity in the acute phase of deep burn injury, rather than a decrease as is commonly believed. Severe burns result in a severe imbalance of the gut flora, with a decrease in probiotics and an increase in microorganisms that trigger inflammation and cognitive deficits, and multiple pathways of metabolism and substance synthesis are affected. Simple machine learning model testing suggests several bacterial genera as potential biomarkers of severe burn phenotypes.
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Quemaduras , Microbioma Gastrointestinal , Microbiota , Humanos , Animales , Ratones , Bacterias/genética , Firmicutes/genética , ARN Ribosómico 16S/genéticaRESUMEN
OBJECTIVES: This study aimed to evaluate the prognostic significance of postoperative Creatine Kinase type M and B (CK-MB) to total Creatine Kinase (CK) ratio (CK-MB/CK) in colorectal cancer (CRC) patients after radical resection. METHODS: This was a single-center retrospective cohort analysis. Subjects were stage I-III CRC patients hospitalized in Sichuan Cancer Hospital from January 2017 to May 2021. Patients were divided into abnormal group and normal group according to whether the CK-MB/CK ratio was abnormal after surgery. Through a comparative analysis of clinical data, laboratory test results, and prognosis differences between the two groups, we aimed to uncover the potential relationship between abnormal CK-MB > CK results and CRC patients. To gauge the impact of CK-MB/CK on overall survival (OS) and disease-free survival (DFS), we employed the multivariable COX regression and LASSO regression analysis. Additionally, Spearman correlation analysis, logistic regression, and receiver-operating characteristic (ROC) curve analysis were conducted to assess the predictive value of the CK-MB/CK ratio for postoperative liver metastasis. RESULTS: Cox regression analysis revealed that the CK-MB/CK ratio was a stable risk factors for OS (HR = 3.82, p < 0.001) and DFS (HR = 2.31, p < 0.001). To distinguish hepatic metastases after surgery, the ROC area under the curve of CK-MB/CK was 0.697 (p < 0.001), and the optimal cut-off value determined by the Youden index was 0.347. CONCLUSIONS: Postoperative abnormal CK-MB/CK ratio predicts worse prognosis in CRC patients after radical resection and serves as a useful biomarker for detecting postoperative liver metastasis.
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Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Anciano , Biomarcadores de Tumor/sangre , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Creatina Quinasa/sangre , Forma MB de la Creatina-Quinasa/sangre , Curva ROC , Adulto , Supervivencia sin EnfermedadRESUMEN
Background: To investigate the clinical efficacy of Castor integrated branched aortic stent graft for the treatment of Stanford type B aortic dissection with insufficient anchoring area. Methods: Retrospective analysis of clinical data of 26 patients with Stanford type B aortic dissection with insufficient anchoring region (<15â mm) treated by Castor branched aortic stent graft from September 2018 to June 2022 at Ganzhou People's Hospital, including 23 acute cases and 3 chronic cases. Results: Surgical procedures were successfully performed in all 26 patients, and during the perioperative period no complications occurred, such as cerebrovascular accident, stenosis or occlusion of left subclavian artery, progression of reverse avulsion of aortic dissection, and paraplegia. During the operation 2 patients had a small amount of type I endoleak, which disappeared during the postoperative follow-up. The other patients had good postoperative follow-up results. Review of the aortic CTA indicated good stent morphology with patency of the left subclavian artery. Conclusions: The Castor integrated branched aortic stent graft expanded the indications for endoluminal treatment for Stanford type B aortic dissection, which can avoid open surgery and has good clinical outcomes.
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BACKGROUND: Plasmapheresis is widely used for severe hypertriglyceridemia-associated acute pancreatitis (HTG-AP) to remove excessive triglycerides from plasma. This study aimed to evaluate whether plasmapheresis could improve the duration of organ failure in HTG-AP patients. METHODS: We analyzed a cohort of patients from a multicenter, prospective, long-running registry (the PERFORM) collecting HTG-AP patients admitted to the study sites within 72 h from the onset of symptoms. This study was based on data collected from November 2020 to March 2023. Patients who had organ failure at enrollment were involved in the analyses. The primary outcome was time to organ failure resolution within 14 days. Multivariable Cox regression model was used to evaluate the association between plasmapheresis and time to organ failure resolution. Directed acyclic graph (DAG) was used to identify potential confounders. RESULTS: A total of 122 HTG-AP patients were included (median [IQR] sequential organ failure assessment (SOFA) score at enrollment, 3.00 [2.00-4.00]). Among the study patients, 46 underwent plasmapheresis, and 76 received medical treatment. The DAG revealed that baseline serum triglyceride, APACHE II score, respiratory failure, cardiovascular failure, and renal failure were potential confounders. After adjusting for the selected confounders, there was no significant difference in time to organ failure resolution between patients undergoing plasmapheresis and those receiving exclusive medical treatment (HR = 1.07; 95%CI 0.68-1.68; P = 0.777). Moreover, the use of plasmapheresis was associated with higher ICU requirements (97.8% [45/46] vs. 65.8% [50/76]; OR, 19.33; 95%CI 2.20 to 169.81; P = 0.008). CONCLUSIONS: In HTG-AP patients with early organ failure, plasmapheresis was not associated with accelerated organ failure resolution compared to medical treatment but may be associated with more ICU admissions. TRIAL REGISTRATION: The PERFORM study was registered in the Chinese Clinical Trial Registry (ChiCTR2000039541). Registered 30 October 2020.
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Epithelial-to-mesenchymal transition (EMT) that endows cancer cells with increased invasive and migratory capacity enables cancer dissemination and metastasis. This process is tightly associated with metabolic reprogramming acquired for rewiring cell status and signaling pathways for survival in dietary insufficiency conditions. However, it remains largely unclear how transcription factor (TF)-mediated transcriptional programs are modulated during the EMT process. Here, we reveal that depletion of a key epithelial TF, ELF3 (E74-like factor-3), triggers a transforming growth factor ß (TGF-ß) signaling activation-like mesenchymal transcriptomic profile and metastatic features linked to the aminoacyl-tRNA biogenesis pathway. Moreover, the transcriptome alterations elicited by ELF3 depletion perfectly resemble an ATF4-dependent weak response to amino acid starvation. Intriguingly, we observe an exclusive enrichment of ELF3 and ATF4 in epithelial and TGF-ß-induced or ELF3-depletion-elicited mesenchymal enhancers, respectively, with rare co-binding on altered enhancers. We also find that the upregulation of aminoacyl-tRNA synthetases and some mesenchymal genes upon amino acid deprivation is diminished in ATF4-depleted cells. In sum, the loss of ELF3 binding on epithelial enhancers and the gain of ATF4 binding on the enhancers of mesenchymal factors and amino acid deprivation responsive genes facilitate the loss of epithelial cell features and the gain of TGF-ß-signaling-associated mesenchymal signatures, which further promote lung cancer cell metastasis.
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Factor de Transcripción Activador 4 , Aminoácidos , Proteínas de Unión al ADN , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Factores de Transcripción , Factor de Crecimiento Transformador beta , Transición Epitelial-Mesenquimal/genética , Factor de Transcripción Activador 4/metabolismo , Factor de Transcripción Activador 4/genética , Humanos , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Aminoácidos/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Línea Celular Tumoral , Transducción de Señal , Proteínas Proto-Oncogénicas c-ets/metabolismo , Proteínas Proto-Oncogénicas c-ets/genética , Transcriptoma , AnimalesRESUMEN
Hypertension is a prominent contributor to vascular injury. Deubiquinatase has been implicated in the regulation of hypertension-induced vascular injury. In the present study we investigated the specific role of deubiquinatase YOD1 in hypertension-induced vascular injury. Vascular endothelial endothelial-mesenchymal transition (EndMT) was induced in male WT and YOD1-/- mice by administration of Ang II (1 µg/kg per minute) via osmotic pump for four weeks. We showed a significantly increased expression of YOD1 in mouse vascular endothelial cells upon Ang II stimulation. Knockout of YOD1 resulted in a notable reduction in EndMT in vascular endothelial cells of Ang II-treated mouse; a similar result was observed in Ang II-treated human umbilical vein endothelial cells (HUVECs). We then conducted LC-MS/MS and co-immunoprecipitation (Co-IP) analyses to verify the binding between YOD1 and EndMT-related proteins, and found that YOD1 directly bound to ß-catenin in HUVECs via its ovarian tumor-associated protease (OTU) domain, and histidine at 262 performing deubiquitination to maintain ß-catenin protein stability by removing the K48 ubiquitin chain from ß-catenin and preventing its proteasome degradation, thereby promoting EndMT of vascular endothelial cells. Oral administration of ß-catenin inhibitor MSAB (20 mg/kg, every other day for four weeks) eliminated the protective effect of YOD1 deletion on vascular endothelial injury. In conclusion, we demonstrate a new YOD1-ß-catenin axis in regulating Ang II-induced vascular endothelial injury and reveal YOD1 as a deubiquitinating enzyme for ß-catenin, suggesting that targeting YOD1 holds promise as a potential therapeutic strategy for treating ß-catenin-mediated vascular diseases.
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Angiotensina II , Células Endoteliales de la Vena Umbilical Humana , Ratones Endogámicos C57BL , Ratones Noqueados , beta Catenina , Animales , beta Catenina/metabolismo , Humanos , Angiotensina II/farmacología , Angiotensina II/metabolismo , Masculino , Ratones , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Endotelial-MesenquimatosaRESUMEN
To reveal the key factors influencing the progression of severe COVID-19 to critical illness and death in the intensive care unit (ICU) and to accurately predict the risk, as well as to validate the efficacy of treatment using traditional Chinese medicine (TCM), thus providing valuable recommendations for the clinical management of patients. A total of 189 patients with COVID-19 in 25 ICUs in Chongqing, China, were enrolled, and 16 eventually died. Statistical models shown that factors influencing the progression of COVID-19 to critical illness include the severity of illness at diagnosis, the mode of respiratory support, and the use of TCM. Risk factors for death include a history of metabolic disease, the use of antiviral drugs and TCM, and invasive endotracheal intubation. The area under curve of the noncollinearity model predicted the risk of progression to critical illness and the risk of death reached 0.847 and 0.876, respectively. The use of TCM is an independent protective factor for the prevention of the progression of severe COVID-19, while uncorrectable hypoxemia and invasive respiratory support are independent risk factors, and antiviral drugs can help reduce mortality. The multifactorial prediction model can assess the risk of critical illness and death in ICU COVID-19 patients, and inform clinicians in choosing the treatment options and medications.
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COVID-19 , Humanos , COVID-19/terapia , Medicina Tradicional China , Enfermedad Crítica/terapia , Unidades de Cuidados Intensivos , AntiviralesRESUMEN
OBJECTIVE: The purpose of this study is to explore the biological mechanism of Schizandrin A (SchA) inducing non-small cell lung cancer (NSCLC) apoptosis. METHODS: The reverse molecular docking tool "Swiss Target Prediction" was used to predict the targets of SchA. Protein-protein interaction analysis was performed on potential targets using the String database. Functional enrichment analyses of potential targets were performed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The conformation of SchA binding to target was simulated by chemical-protein interactomics and molecular docking. The effect of SchA on the expression and phosphorylation level of EGFR was detected by Western blot. Lipofectamine 3000 and EGFR plasmids were used to overexpress EGFR. Apoptosis was tested with Annexin V-FITC and propidium iodide staining, and cell cycle was detected by propidium iodide staining. RESULTS: The "Swiss Target Prediction" database predicted 112 and 111 targets based on the 2D and 3D structures of SchA, respectively, of which kinases accounted for the most, accounting for 24%. Protein interaction network analyses showed that molecular targets such as ERBB family and SRC were at the center of the network. Functional enrichment analyses indicated that ERBB-related signaling pathways were enriched. Compound-protein interactomics and molecular docking revealed that SchA could bind to the ATP-active pocket of the EGFR tyrosine kinase domain. Laboratory results showed that SchA inhibited the phosphorylation of EGFR. Insulin could counteract the cytotoxic effect of SchA. EGFR overexpression and excess EGF or IGF-1 had limited impacts on the cytotoxicity of SchA. CONCLUSIONS: Network pharmacology analyses suggested that ERBB family members may be the targets of SchA. SchA can inhibit NSCLC at least in part by inhibiting EGFR phosphorylation, and activating the EGFR bypass can neutralize the cytotoxicity of SchA.