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1.
Vet Microbiol ; 279: 109662, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36736169

RESUMO

Duck circovirus (DuCV) is one of the most prevalent infectious viruses in the duck industry in China. Although the clinical symptoms vary, it often causes immunosuppression in the host and leads to secondary infection with other pathogens. Fowl adenovirus serotype 4 (FAdV-4) mainly infects chickens and causes hydropericardium hepatitis syndrome. However, the incidence of infection in ducks has increased in recent years, and the phenomenon of mixed infection with DuCV is very common, resulting in more severe clinical morbidity. However, there is no systematic study evaluating the presence of mixed infection. To explore the synergistic pathogenicity of DuCV and FAdV-4 co-infection in Cherry Valley ducks, a comparative experiment was established between DuCV and FAdV-4 co-infection and single infection animal models. It was found that DuCV and FAdV-4 co-infected ducks showed more pronounced clinical signs of pericardial effusion, hepatitis and immunosuppression; more severe tissue damage in target organs; and more significant levels of viral load, biochemical indicators and immune indicators in various organs compared with Cherry Valley ducks infected with just one virus. The results showed that co-infection with DuCV and FAdV-4 may promote greater viral replication, causing more severe tissue damage and immunosuppression than infection with just one virus. Therefore, the monitoring and prevention of the two viruses should be strengthened clinically, with a particular focus on the potential harm of DuCV as it carries the highest infection rate.

2.
Colloids Surf B Biointerfaces ; 223: 113159, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36736174

RESUMO

Polypropylene (PP) mesh has been widely used in hernia repair as prosthesis material owing to its excellent balanced biocompatibility and mechanical properties. However, abdominal adhesion between the visceral and PP mesh is still a major problem. Therefore, anti-adhesive PP mesh was designed with poly(vinyl alcohol) (PVA) hydrogel and liposomes drug delivery system. First, PVA hydrogel coating was formed on the surface of PP mesh with freezing-thawing processing cycles (FTP). Subsequently, the lyophilized PVA10-c-PP was immersed in rapamycin (RPM)-loaded liposome solution until swelling equilibrated to obtain the anti-adhesion mesh RPM@LPS/PVA10-c-PP. It was demonstrated that the hydrogel coating can stably fix on the surface of PP mesh even after immersed in PBS solution at 37 °C or 40 °C for up to 30 days. In vitro cell tests revealed the excellent cytocompatibility and the potential to inhibit cell adhesion of the modified PP mesh. Moreover, the anti-adhesive effects of the RPM@LPS/PVA10-c-PP mesh was evaluated through in vivo experiments. The RPM@LPS/PVA10-c-PP mesh exhibited less adhesion than original PP mesh throughout the duration of implantation. At 30 days, the adhesion score of RPM@LPS/PVA10-c-PP mesh was 1.37 ± 0.75, however the original PP was 3 ± 0.71. Furthermore, the results of H&E and Masson trichrome staining proved that the RPM@LPS/PVA10-c-PP mesh showed slighter inflammation response and significant looser fibrous tissue surrounded the PP filaments as compared to the native PP. The current findings manifested that this type of RPM@LPS/PVA10-c-PP might be a potential candidate for anti-adhesion treatment. DATA AVAILABILITY: Data will be made available on request.

3.
Carbohydr Polym ; 305: 120543, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36737194

RESUMO

Postoperative peritoneal adhesions are common complications caused by abdominal and pelvic surgery, which seriously impact the quality of life of patients and impose additional financial burdens. Using of biomedical materials as physical barriers to completely isolate the traumatic organ and injured tissue is an optimal strategy for preventing postoperative adhesions. However, the limited efficacy and difficulties in the complete degradation or integration of biomedical materials with living tissues restrict the application of these materials. In this study, novel chitin-based crosslinked hydrogels with appropriate mechanical properties and flexibilities were developed using a facile and green strategy. The developed hydrogels simultaneously exhibited excellent biocompatibilities and resistance to nonspecific protein adsorption and NIH/3T3 fibroblast adhesion. Furthermore, these hydrogels were biodegradable and could be completely integrated into the native extracellular matrix. The chitin-based crosslinked hydrogels also effectively inhibited postoperative peritoneal adhesions in rat models of adhesion and recurrence. Therefore, these novel chitin-based crosslinked hydrogels are excellent candidate physical barriers for the efficient prevention of postoperative peritoneal adhesions and provide a new anti-adhesion strategy for biomedical applications.

4.
Cardiorenal Med ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36724747

RESUMO

INTRODUCTION: Heart valvular calcification (HVC) is an important predictor of cardiovascular events (CEs) and all-cause mortality in dialysis patients. Patients in the early stage of dialysis or those with central venous catheters (CVCs) are also at high risk of cardiovascular and all-cause mortality. It could be a confounding factor for the prognosis of HVC on CE. METHODS: From March 2017 to April 2022, the prognosis of HVC on CE and all-cause mortality was studied retrospectively in 158 hemodialysis (HD) patients who used arteriovenous fistulas (AVFs) or arteriovenous grafts (AVGs) as vascular access and entered HD for more than 12 months. RESULTS: Out of 158 patients, 70 (44.3%) were diagnosed with HVC via echocardiography. A total of 180 CEs occurred during follow-up. Among them, acute heart failure (AHF) accounted for 62.66%, and its prevalence was significantly higher in the HVC group than that in the non-HVC group (p <0.0001). The cumulative incidence of CE-free survival in the HVC group was significantly lower than that in the non-HVC group (p = 0.030). Only 11 patients died and there was no significant difference in all-cause mortality between the two groups (p = 0.560). Multivariate COX regression analyses showed that HD vintage, mitral valve calcification (MVC), and aortic valve regurgitation (AR)/aortic valve stenosis (AS) but not aortic valve calcification (AVC) were risk factors for CE (p <0.05). CONCLUSION: After excluding the factors of the early stage of HD and CVC, HVC remained a predictor of adverse CE in HD patients.

5.
ACS Sens ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36726333

RESUMO

Developing highly efficient gas sensors with excellent performance for rapid and sensitive detection of volatile organic compounds (VOCs) is of critical importance for the protection of human health, ecological environment, and other factors. Here, a robust gas sensor based on Raman technology was constructed by an in situ grown 2D covalent organic framework (COF) on Au nanoparticles' surface in the microchannel. Dual enhancement effects are included for the as-prepared microfluidic sensor. First, acting as a gas confinement chamber, the 2D COF could effectively capture gas molecules with high adsorption capacity and fast adsorption kinetics, resulting in VOCs' preconcentration at a high level in the COF layer. At the same time, after being stacked in the microchannel, abundant hot spots were generated among the nanogaps of Au@COF NPs. The local surface plasmon resonance effect could effectively enhance the Raman intensity. Both factors contribute to the improved detection sensitivity of VOCs. As a demonstration, several representative VOCs with different functional groups were tested. The resultant Raman spectra were subjected to the statistical principal component analysis. Varied VOCs can be successfully detected with a detection limit as low as ppb level and distinguished with 95% confidence interval. The present microfluidic platform provides a simple, sensitive, and fast method for VOCs' sensing and distinguishing, which is expected to hold potential applications in the fields of health, agricultural, and environmental research.

7.
J Hazard Mater ; 447: 130788, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36682251

RESUMO

Combined pollution from microplastics (MPs) and cadmium (Cd) can influence soil environment and soil biota, altering plant growth and development, and Cd mobilization. We investigated the effects of polystyrene (PS) and polypropylene (PP) MPs alongside Cd on soil Cd bioavailability, rhizosphere soil metabolomics, bacterial community structure, and maize (Zea mays L.) growth in two soil types (red soil and cinnamon soil). Although the addition of PS/PP-Cd promoted Cd accumulation in maize plants overall, there were large-particle-size- and small-particle-size-dependent effects in the red soil and cinnamon soil, respectively. The difference is mainly due to the capacity of the large particle size MPs to significantly reduce soil pH, improve soil electrical conductivity (EC), promote active Cd, and intensify Cd mobilization in red soil. In contrast, small-size MPs in cinnamon soil promoted the synthesis and secretion of rhizosphere amino acids and soil metabolites, thus promoting Cd absorption by maize roots. Soil microorganisms also improved Cd bioavailability via C-related functional bacteria. Overall, our study provides novel insights on the potential effects of combined MPs and Cd pollution on soil ecology and agricultural production, enhancing our understanding of rhizosphere metabolites in different soils.

8.
Int J Infect Dis ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36682682

RESUMO

OBJECTIVES: To evaluate the safety, immunogenicity and lot-to-lot consistency of sIPV in a 5-dose vial presentation. METHODS: Stage 1 was an open-label safety observation, in which 72 healthy subjects (incl., 24 adults, children, and infants each) were given one or three doses of the 5-dose vial sIPV; stage 2 was a randomized, blinded and positive-control study, in which 1,500 infants were randomized at the ratio of 1:1:1:1:1 into 5 groups to receive either three doses of the 5-dose sIPV three lots, a conventional IPV or a single-dose sIPV as controls, for primary immunization. Safety, immunogenicity and lot-to-lot consistency were assessed. RESULTS: Among 1,456 subjects completed the primary immunization, the GMT ratios of types 1,2,3 of each pair of lots were all within the equivalence criteria margin (0.67-1.50). The seroconversion rates of types 1,2,3 in the combined test group were 98.02%, 94.07%, and 98.77% respectively, non-inferior to both control groups. The overall incidence of adverse reactions (ARs) was 29.68% and erythema was the most common ARs with incidences of 10.47%,9.33%, and 9.73% in the combined test group, and control groups (p>0.05). CONCLUSIONS: The 5-dose sIPV demonstrated good safety, immunogenicity, and lot-to-lot consistency. REGISTRATION: This study has been registered at ClinicalTrials.gov (NCT05386810).

9.
Artigo em Inglês | MEDLINE | ID: mdl-36651564

RESUMO

Here, we report the first example of Ni-catalyzed asymmetric hydrosilylation of 1,1-disubstituted allenes with high level of regioselectivities and enantioselectivities. The key to achieve this stereoselective hydrosilylation reaction was the development of the SPSiOL-derived bisphosphite ligands (SPSiPO). This protocol features broad substrate scope, excellent functional group, and heterocycle tolerance, thus provides a versatile method for the construction of enantioenriched tertiary allylsilanes in a straightforward and atom-economic manner. DFT calculations were performed to reveal the reaction mechanism and the origins of the enantioselectivity.

10.
Ren Fail ; 45(1): 2151468, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36645039

RESUMO

BACKGROUND: Although current guidelines didn't support the routine use of furosemide in oliguric acute kidney injury (AKI) management, some patients may benefit from furosemide administration at an early stage. We aimed to develop an explainable machine learning (ML) model to differentiate between furosemide-responsive (FR) and furosemide-unresponsive (FU) oliguric AKI. METHODS: From Medical Information Mart for Intensive Care-IV (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD), oliguric AKI patients with urine output (UO) < 0.5 ml/kg/h for the first 6 h after ICU admission and furosemide infusion ≥ 40 mg in the following 6 h were retrospectively selected. The MIMIC-IV cohort was used in training a XGBoost model to predict UO > 0.65 ml/kg/h during 6-24 h succeeding the initial 6 h for assessing oliguria, and it was validated in the eICU-CRD cohort. We compared the predictive performance of the XGBoost model with the traditional logistic regression and other ML models. RESULTS: 6897 patients were included in the MIMIC-IV training cohort, with 2235 patients in the eICU-CRD validation cohort. The XGBoost model showed an AUC of 0.97 (95% CI: 0.96-0.98) for differentiating FR and FU oliguric AKI. It outperformed the logistic regression and other ML models in correctly predicting furosemide diuretic response, achieved 92.43% sensitivity (95% CI: 90.88-93.73%) and 95.12% specificity (95% CI: 93.51-96.3%). CONCLUSION: A boosted ensemble algorithm can be used to accurately differentiate between patients who would and would not respond to furosemide in oliguric AKI. By making the model explainable, clinicians would be able to better understand the reasoning behind the prediction outcome and make individualized treatment.


Assuntos
Injúria Renal Aguda , Furosemida , Humanos , Estudos Retrospectivos , Oligúria/diagnóstico , Oligúria/tratamento farmacológico , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/tratamento farmacológico , Aprendizado de Máquina
11.
Cell Signal ; 105: 110593, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36682592

RESUMO

Tracheal fibrosis is a key abnormal repair process leading to fatal stenosis, characterized by excessive fibroblast activation and extracellular matrix (ECM) deposition. GATA6, a zinc finger-containing transcription factor, is involved in fibroblast activation, while its role in tracheal fibrosis remains obscure. The present study investigated the potential role of GATA6 as a novel regulator of tracheal fibrosis. It was found that GATA6 and α-smooth muscle actin (α-SMA) were obviously increased in tracheal fibrotic granulations and in TGFß1-treated primary tracheal fibroblasts. GATA6 silencing inhibited TGFß1-stimulated fibroblast proliferation and ECM synthesis, promoted cell apoptosis, and inactivated Wnt/ß-catenin pathway, whereas GATA6 overexpression showed the reverse effects. SKL2001, an agonist of Wnt/ß-catenin signaling, restored collagen1a1 and α-SMA expression which was suppressed by GATA6 silencing. Furthermore, in vivo, knockdown of GATA6 ameliorated tracheal fibrosis, as manifested by reduced tracheal stenosis and ECM deposition. GATA6 inhibition in rat tracheas also impaired granulation proliferation, increased apoptosis, and inactivated Wnt/ß-catenin pathway. In conclusion, our findings indicate that GATA6 triggers fibroblast activation, cell proliferation, and apoptosis resistance in tracheal fibrosis via the Wnt/ß-catenin signaling pathway. Targeting GATA6 may represent a promising therapeutic approach for tracheal fibrosis.

12.
Comp Biochem Physiol C Toxicol Pharmacol ; 266: 109556, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36709861

RESUMO

Aquatic animals suffer from heat and hypoxia stress more frequently due to global climate change and other anthropogenic activities. Heat and hypoxia stress can significantly affect mitochondrial function and energy metabolism. Here, the response and adaptation characteristics of mitochondria and energy metabolism in the gill of the hard clam Mercenaria mercenaria under heat (35 °C), hypoxia (0.2 mg/L), and heat plus hypoxia stress (35 °C, 0.2 mg/L) after 48 h exposure were investigated. Mitochondrial membrane potentials were depolarized under environmental stress. Mitochondrial fusion, fission and mitophagy played a key role in maintain mitochondrion function. The AMPK subunits showed different expression under environmental stress. Acceleration of enzyme activities (phosphofructokinase, pyruvate kinase and lactic dehydrogenase) and accumulation of anaerobic metabolites in glycolysis and TCA cycle implied that the anaerobic metabolism might play a key role in providing energy. Accumulation of amino acids might help to increase tolerance under heat and heat combined hypoxia stress. In addition, urea cycle played a key role in amino acid metabolism to prevent ammonia/nitrogen toxicity. This study improved our understanding of the mitochondrial and energy metabolism responses of marine bivalves exposed to environmental stress.

13.
J Neurochem ; 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36718502

RESUMO

Tryptophan (Trp) metabolism has been implicated in neuroinflammatory and neurodegenerative disorders, but its relationship with neuromyelitis optica spectrum disorders (NMOSDs) is unclear. In this pilot study, cerebrospinal fluid (CSF) was prospectively collected from 26 NMOSD patients in relapse and 16 controls with noninflammatory diseases, and 6 neurometabolites in the tryptophan metabolic pathway, including 5-hydroxytryptamine (5-HT), kynurenine (KYN), melatonin (MLT), 5-hydroxyindoleacetic acid (5HIAA), 3-hydroxy-o-aminobenzoic acid (3-HAA), and kynurenic acid (KYA), were measured by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The association of Trp metabolites with NMOSD and its clinical parameters was evaluated. The role of KYN, which is a Trp metabolite involved in the binding of NMOSD-IgG antibody to aquaporin 4 (AQP4), was also evaluated in vitro. CSF KYN was significantly decreased in patients with relapsing NMOSD compared to controls, and CSF KYN was associated with CSF white blood cells in NMOSD. In vitro experiments showed that NMOSD-IgG specifically recognized KYN, which reversed the NMOSD-IgG-induced downregulation of AQP4 expression. Our results show that abnormal Trp metabolism occurs in NMOSD and that KYN might be a potential target for the treatment of AQP4-IgG-positive NMOSD patients.

14.
J Med Internet Res ; 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36719823

RESUMO

BACKGROUND: Despite the increased development and use of mobile health (mHealth) devices during the COVID-19 pandemic, there is little knowledge of Chinese willingness to use mHealth devices and the key factors associated with their usage in the post-COVID-19 era. Therefore, a more comprehensive and multi-angle investigation is necessary. OBJECTIVE: The purpose of this study was to probe Chinese attitudes regarding the use of mHealth and analyze possible associations between the attitude of willingness to use mHealth devices and some factors based on the socioecological model (SEM). METHODS: A survey was conducted by quota sampling to recruit participants from 148 cities in China between 20 June 2022 and 31 August 2022. Data from the survey were analyzed using multiple stepwise regression to examine the factors associated with the willingness to use mHealth devices. Standardized regression coefficients (ß) and 95% confidence intervals (CIs) were calculated using multiple stepwise regression. RESULTS: The survey contained 21916 questionnaires collection, and 21897 were valid questionnaires, with a 99.91% effective rate. The median score of willingness to use mHealth in the post-COVID-19 era was 70 points on a scale of 0-100. Multiple stepwise regression results showed that female (ß = 0.03; 95% CI 1.04-2.35), openness personality trait (ß = 0.05; 95% CI 0.53-0.96), higher household per capita monthly income (ß = 0.03; 95% CI 0.77-2.24), commercial and multiple insurance (ß = 0.04; 95% CI 1.77-3.47) were the associated factors of willingness to use mHealth devices. Additionally, people with high scores of health literacy (ß = 0.13; 95% CI 0.53-0.68), self-reported health rating (ß = 0.22; 95% CI 0.24-0.27), social support (ß = 0.08; 95% CI 0.40-0.61), family health (ß = 0.03; 95% CI 0.03-0.16), neighbor relations (ß = 0.12; 95% CI 2.09-2.63), and family social status (ß = 0.07; 95% CI 1.19-1.69) were more likely to use mHealth devices. CONCLUSIONS: Based on the theoretical framework of SEM, this study identified factors specifically associated with Chinese willingness to use mHealth devices in the post-COVID-19 era. These findings provide reference information for the research, development, promotion, and application of future mHealth devices.

15.
Int J Biol Macromol ; 231: 123319, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36682666

RESUMO

The aggregation of amyloid proteins is highly related to the occurrence and development of neurodegenerative and metabolic diseases. The detection of amyloid fibrils or monitoring fibrillation process would be necessary to understand the fundamental knowledge about the diseases and further facilitate the research for the drug discovery and disease treatment. In this study, three proto-berberine alkaloids, i.e. berberine, palmatine and coptisine, were examined as three distinctive fluorescent probes to detect amyloid fibrils. These three alkaloids were found to be sensitive to the microenvironment, i.e. viscosity and polarity, with varied fluorescence intensity. They could sensitively probe insulin and lysozyme fibrils with turn-on fluorescence, but did not respond to protein monomers, merited with advantages of larger Stokes shift, greenish-yellow fluorescence and no interference with the fibrillation process. Hydrophobic, electrostatic and hydrogen bond interactions were explored to exist between alkaloids and the fibrils. Moreover, these alkaloids succeeded in monitoring the aggregation process of amyloid proteins in vitro and imaging the fibrils in living cells. The present study demonstrates that the three alkaloids could be the potential candidate fluorescent probes for amyloid fibrils.

16.
Radiat Oncol ; 18(1): 12, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36658595

RESUMO

OBJECTIVE: The purpose of this study is to verify the correlation between medium and low radiation doses of the pelvic-bone marrow and the incidence of lymphocytic toxicity during concurrent chemoradiotherapy for cervical cancer. MATERIALS AND METHODS: This research included 117 cervical cancer patients, who received concurrent chemoradiotherapy. Radiotherapy included external-beam radiation therapy and brachytherapy. The dosimetry parameters include the Volume receiving 5 Gy (V5), 10 Gy (V10), 20 Gy (V20), 30 Gy (V30), 40 Gy (V40), 50 Gy (V50), and the mean dose (D mean) of the bone marrow. Lymphocytic toxicity was calculated from lowest lymphocytic count after two cycles of concurrent chemotherapy. RESULTS: During concurrent chemoradiotherapy, the incidence of lymphocytic toxicity is 94.88%. The incidence of grade 3-4 toxicity is 68.38%. Multivariate analysis findings show that the dosimetry parameters V5, V10, V20, and V30 are significantly correlated with lymphocytic toxicity. The patients are divided into small-volume subgroups and large-volume subgroups based on the cutoff values. The relative risk of both grade 1-4 and grade 3-4 lymphocytic toxicity is significantly lower in the small-volume subgroups than in the large-volume subgroups (P < 0.05). Kaplan-Meier analysis shows that the incidence of both grade 1-4 and grade 3-4 lymphocytic toxicity of the small-volume subgroups is significantly lower than that of the large-volume subgroups (P < 0.05). CONCLUSION: There is a significant correlation between a medium and low dose of pelvic-bone-marrow radiation and incidence of lymphocytic toxicity. Reducing the volume of medium and low radiation doses could effectively reduce incidence of lymphocytic toxicity.


Assuntos
Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero , Feminino , Humanos , Medula Óssea , Radioterapia de Intensidade Modulada/efeitos adversos , Dosagem Radioterapêutica , Neoplasias do Colo do Útero/radioterapia , Quimiorradioterapia/efeitos adversos , Doses de Radiação
17.
J Cardiovasc Dev Dis ; 10(1)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36661924

RESUMO

BACKGROUND: The incidence of acute myocardial infarction (AMI) in the younger population has been increasing gradually in recent years. The objective of the present study is to investigate the safety and effectiveness of drug-eluting balloons (DEBs) in young patients with AMI. METHODS: All consecutive patients with AMI aged ≤ 45 years were retrospectively enrolled. The primary endpoint was a device-oriented composite endpoint (DOCE) of cardiac death, target vessel myocardial infarction (MI), or target lesion revascularization (TLR). The secondary study endpoints included heart failure and major bleeding events. RESULTS: A total of 276 young patients presenting with AMI were finally included. The median follow-up period was 1155 days. Patients treated with DEBs had a trend toward a lower incidence of DOCEs (3.0% vs. 11.0%, p = 0.12) mainly driven by the need for TLR (3.0% vs. 9.1%, p = 0.19) than those treated with DESs. No significant differences between the two groups were detected in the occurrence of cardiac death (0.0% vs. 0.5%, p = 0.69), MI (0.0% vs. 1.4%, p = 0.40), heart failure (0.0% vs. 1.9%, p = 0.39), or major bleeding events (1.5% vs 4.8%, p = 0.30). Multivariate regression analysis showed that DEBs were associated with a trend toward a lower risk of DOCEs (HR 0.13, 95% CI [0.02, 1.05], p = 0.06). CONCLUSIONS: The findings of the present study suggested that DEBs might be a potential treatment option in young patients with AMI. A larger scale, randomized, multicenter study is required to investigate the safety and effectiveness of DEBs in this setting.

18.
J Clin Med ; 12(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36675362

RESUMO

BACKGROUND: Ischemia reperfusion injury (IRI) remains a major problem in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). We have developed a novel reperfusion strategy for PCI and named it "volume-controlled reperfusion (VCR)". The aim of the current study was to assess the safety and feasibility of VCR in patients with STEMI. METHODS: Consecutive patients admitted to Beijing Chaoyang Hospital with STEMI were prospectively enrolled. The feasibility endpoint was procedural success. The safety endpoints included death from all causes, major vascular complications, and major adverse cardiac event (MACE), i.e., a composite of cardiac death, myocardial reinfarction, target vessel revascularization (TVR), and heart failure. RESULTS: A total of 30 patients were finally included. Procedural success was achieved in 28 (93.3%) patients. No patients died during the study and no major vascular complications or MACE occurred during hospitalization. With the exception of one patient (3.3%) who underwent TVR three months after discharge, no patient encountered death (0.0%), major vascular complications (0.0%), or and other MACEs (0.0%) during the median follow-up of 16 months. CONCLUSION: The findings of the pilot study suggest that VCR has favorable feasibility and safety in patients with STEMI. Further larger randomized trials are required to evaluate the effectiveness of VCR in STEMI patients.

19.
Proc Natl Acad Sci U S A ; 120(5): e2218663120, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36689655

RESUMO

Complex systems can exhibit sudden transitions or regime shifts from one stable state to another, typically referred to as critical transitions. It becomes a great challenge to identify a robust warning sufficiently early that action can be taken to avert a regime shift. We employ landscape-flux theory from nonequilibrium statistical mechanics as a general framework to quantify the global stability of ecological systems and provide warning signals for critical transitions. We quantify the average flux as the nonequilibrium driving force and the dynamical origin of the nonequilibrium transition while the entropy production rate as the nonequilibrium thermodynamic cost and thermodynamic origin of the nonequilibrium transition. Average flux, entropy production, nonequilibrium free energy, and time irreversibility quantified by the difference in cross-correlation functions forward and backward in time can serve as early warning signals for critical transitions much earlier than other conventional predictors. We utilize a classical shallow lake model as an exemplar for our early warning prediction. Our proposed method is general and can be readily applied to assess the resilience of many other ecological systems. The early warning signals proposed here can potentially predict critical transitions earlier than established methods and perhaps even sufficiently early to avert catastrophic shifts.


Assuntos
Ecossistema , Física , Termodinâmica , Entropia
20.
Carcinogenesis ; 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36591938

RESUMO

Pancreatic cancer (PaCa) is one of the most fatal malignancies of the digestive system, and most patients are diagnosed at advanced stages due to the lack of specific and effective tumor-related biomarkers for the early detection of PaCa. miR-492 has been found to be upregulated in PaCa tumor tissue and may serve as a potential therapeutic target. However, the molecular mechanisms by which miR-492 promotes PaCa tumor growth and progression are unclear. In this study, we first found that miR-492 in enhancer loci activated neighboring genes (NR2C1/NDUFA12/TMCC3) and promoted PaCa cell proliferation, migration, and invasion in vitro. We also observed that miR-492-activating genes significantly enriched the TGF-ß/Smad3 signaling pathway in PaCa to promote epithelial-mesenchymal transition (EMT) during tumorigenesis and development. Using CRISPR-Cas9 and ChIP assays, we further observed that miR-492 acted as an enhancer trigger, and that antagomiR-492 repressed PaCa tumorigenesis in vivo, decreased the expression levels of serum TGF-ß, and suppressed the EMT process by downregulating the expression of NR2C1. Our results demonstrate that miR-492, as an enhancer trigger, facilitates PaCa progression via the NR2C1-TGF-ß/Smad3 pathway.

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