RESUMEN
Sichuan cuisine was previously fitted into the Chinese Heart-Healthy Diet (CHH) trial to verify the antihypertensive effect. Whether the modified Sichuan diet lessens cardiovascular disease (CVD) is not fully explored. We aimed to estimate the effects of the Sichuan version of CHH diet (CHH diet-SC) on the 10-year risk of CVD and vascular age. A single-blinded randomised controlled feeding trial was conducted. General CVD prediction model was used in manners of intention-to-treat and per-protocol set. After a 7-d run-in period, fifty-three participants with pre- and grade I hypertension from local communities were randomised and provided with either CHH diet-SC (n 27) or a control diet (n 26) for 4 weeks. Mean absolute and relative estimated CVD risks were reduced by 4·5 % and 27·9 % in the CHH diet-SC group, and the between-group relative risk reduction was 19·5 % (P < 0·001) using linear mixed-effects models. The sensitivity analysis with datasets and models showed consistent results, and pre-specified factors were not associated with the intervention effects. The vascular age of CHH-SC group was theoretically 4·4 years younger than that of the control group after intervention. Compared with a typical diet, adopting the CHH diet-SC over 1 month significantly reduced 10-year CVD risks and vascular ages among local adults with mild hypertension.
Asunto(s)
Enfermedades Cardiovasculares , Hipertensión , Adulto , Humanos , Preescolar , Dieta Saludable , Enfermedades Cardiovasculares/prevención & control , Dieta , Hipertensión/prevención & control , China/epidemiologíaRESUMEN
Myocardial infarction (MI) is one of the leading causes of death. This is attributed to the dramatic changes in the myocardial microenvironment post-MI. Therefore, effective intervention in the early stages of MI is significant for inhibiting its progression and improving cardiac function. Herein, an injectable composite hydrogel scaffold (Gel-pBP@Mg) was developed by integrating magnesium (Mg)-modified black phosphorus nanosheets (pBP@Mg) into a reactive oxygen species-responsive hydrogel (Gel). This loose and porous Gel provides a natural platform for carrying pBP@Mg. In situ, sustained release of pBP@Mg is achieved via responsive ROS degradation in the infarct site. The high ROS reactivity of Black phosphorus nanosheets (BPNSs) can effectively inhibit the progression of oxidative stress in the infarct area and reduce inflammatory response by down-regulating the NF-κB pathway. Additionally, the sustained release of Mg loaded on the surface of BPNSs can effectively promote angiogenesis in MI, which is significant for the long-term prognosis after infarction. Our developed Gel-pBP@Mg effectively blocked infarction progression and improved myocardial function by sustainably inhibiting the "oxidative stress-inflammation" reaction chain and pro-angiogenesis. This study reveals Gel-pBP@Mg composite therapeutic potential in treating MI through In vitro and In vivo studies, providing a promising modality for MI treatment.
Asunto(s)
Antioxidantes , Infarto del Miocardio , Estrés Oxidativo , Fósforo , Especies Reactivas de Oxígeno , Animales , Masculino , Ratones , Angiogénesis , Antioxidantes/farmacología , Antioxidantes/química , Hidrogeles/química , Magnesio/química , Magnesio/farmacología , Infarto del Miocardio/tratamiento farmacológico , Nanoestructuras/química , Neovascularización Fisiológica/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fósforo/química , Especies Reactivas de Oxígeno/metabolismoRESUMEN
OBJECTIVE: To determine whether the Chinese heart-healthy diet (Sichuan cuisine version) (CHH diet-SC) was more expensive than the conventional Sichuan diet and explore the food groups and nutrients that mainly affected the cost of CHH diet-SC. DESIGN: Cost analysis of 4-week intervention diets in the Sichuan center representing southwestern China in the CHH diet study. SETTING: A multicentre, parallel-group, single-blind, randomised feeding trial evaluating the efficacy of lowering blood pressure with the cuisine-based CHH diet. PARTICIPANTS: Totally, fifty-three participants with hypertension aged 25-75 years in the Sichuan center were randomised into the control group (n 26) or the CHH diet-SC group (n 27). RESULTS: The CHH diet-SC was more expensive than the control diet (¥27·87 ± 2·41 v. ¥25·18 ± 2·79 equals $3·90 ± 0·34 v. $3·52 ± 0·39, P < 0·001), and the incremental cost-effectiveness ratio for a 1-mm Hg systolic blood pressure reduction was ¥9·12 ($1·28). Intakes and the cost of seafood, dairy products, fruits, soybeans and nuts, whole grains and mixed beans were higher for the CHH diet-SC than for the control diet (P < 0·001). Intakes of vitamin B1, vitamin B6, vitamin C, Mg and phosphorus were positively correlated with the cost (P < 0·05). CONCLUSIONS: The CHH diet-SC costs more than the conventional Sichuan diet, partly due to the high cost of specific food groups. Positive correlations between the intakes of vitamin B1, vitamin B6, vitamin C, Mg, phosphorus and the dietary cost could be a direction to adjust the composition within the food groups to reduce the cost of the CHH diet-SC.
Asunto(s)
Dieta Saludable , Hipertensión , Humanos , Ácido Ascórbico , China , Dieta/economía , Dieta Saludable/economía , Fósforo , Método Simple Ciego , Tiamina , Vitamina B 6 , Vitaminas , Adulto , Persona de Mediana Edad , Anciano , Hipertensión/dietoterapiaRESUMEN
BACKGROUND AND OBJECTIVES: Sichuan cuisine is characterized by high salt and oil content. We aimed to evaluate the effects of the Sichuan cuisine version of Chinese heart-healthy diet (CHH diet-SC) on blood pressure reduction among hypertensive adults. METHODS AND STUDY DESIGN: The Chinese heart-healthy diet (CHH) trial was a multicenter randomized controlled feeding trial among Chinese hypertensive people. We conducted a secondary analysis of the CHH trial using data from the Sichuan center in Southwest China. Fifty-three people aged 25 to 75 years with a mean systolic blood pressure (SBP) between 130 and 159 mmHg were enrolled. Eligible participants underwent a 1-week run-in period with the typical local diet and were randomized 1:1 to consume the CHH diet-SC (n=27) or typical local diet (n=26) for the next 4-week. The primary outcome was the net change in SBP, the secondary outcomes included diastolic blood pressure (DBP), mean arterial pressure (MAP), and the rate of BP control. RESULTS: Compared with the control group, the CHH diet-SC decreased cooking salt, oil, and red meat content and increased inclusion of whole grains, fruits, seafood, low-fat dairy, soybean, and nuts; the SBP experienced reductions of 7.54, 8.60, 9.14, and 10.1 mmHg at the end of weeks 1 through 4; the DBP was reduced 4.01 mmHg at week 4; the MAP was significantly reduced 6.02 mmHg finally; and rate of BP control significantly increased (p<0.05). CONCLUSIONS: Adoption of the CHH diet-SC for 4 weeks can significantly reduce BP and increase the rate of BP control in hypertensive adults.
Asunto(s)
Hipertensión , Hipotensión , Adulto , Humanos , Presión Sanguínea , Dieta , Dieta Saludable , Cloruro de Sodio Dietético , Persona de Mediana Edad , AncianoRESUMEN
Objective: To investigate and analyze the current status and challenges of infant and toddler nutritional services in urban and rural medical facilities in Sichuan Province. Methods: In 2022, a questionnaire survey was conducted to collect data on infant and toddler nutritional services, including feeding guidance, physical growth assessment, and micronutrient deficiency screening, as well as information on personnel and tools in medical facilities throughout Sichuan Province. The provision of nutritional services was analyzed and the urban-rural disparities were assessed. Results: A total of 2206 medical facilities (29.1% from urban areas and 70.9% from rural areas) were investigated. Only 35.8% of medical facilities provided all three types of nutritional services. Specifically, the overall service provision rates were high for feeding guidance (94.6%) and physical growth assessment (85.0%), but lower for micronutrient deficiency screening (37.4%). Rural facilities exhibited significantly lower rates than their urban counterparts for both physical growth assessment and micronutrient deficiency screening (P<0.05). The provision rates of feeding guidance ranged from 70.6% to 93.2%, with responsive feeding guidance being the least implemented (70.6%), particularly in rural areas compared to urban areas (P<0.05). Rates for physical growth assessment and micronutrient deficiency screening ranged from 75.3% to 81.8% and 23.6% to 30.8%, respectively, both showing lower rates in rural settings compared to urban ones (P<0.05). Nutrition service providers were predominantly nurses (52.3%) and clinical practitioners (43.4%). The availability of dietary assessment tools ranged from 7.7% to 15.9%, significantly lower in rural areas compared to urban areas (P<0.001), while physical measurement tools were widely available at rates of 94.6% to 98.5%. Conclusion: At present, the infant and toddler nutritional service provisions of medical facilities in Sichuan Province are incomplete, particularly so in the implementation of feeding guidance, physical growth assessment, and micronutrient deficiency screening. There is a notable shortage of personnel and necessary tools, with rural areas facing more significant challenges. Enhancing the overall capacity of infant and toddler nutritional services in Sichuan Province is essential, with specific attention needed for rural healthcare settings.
Asunto(s)
Población Rural , Humanos , Lactante , China , Estudios Transversales , Preescolar , Encuestas y Cuestionarios , Población Urbana , Micronutrientes/deficiencia , Instituciones de Salud/estadística & datos numéricos , Masculino , Servicios de Salud Rural/estadística & datos numéricos , FemeninoRESUMEN
A flexible asymmetric synthesis of both enantiomers of euphopilolide (1) and jolkinolide E (2) [(+)-and (-)-1, (+)-and (-)-2] has been accomplished. This synthesis features an intramolecular oxa-Pauson-Khand reaction (o-PKR) to expeditiously construct the challenging tetracyclic [6.6.6.5] abietane-type diterpene framework, elegantly showcasing the complexity-generating features of o-PKR synthetic methodology leveraging on a judiciously chosen suitable chiral pool scaffold. Furthermore, the anti-hepatocellular carcinoma (HCC) activity of synthetic (-)-euphopilolide (1), (-)-jolkinolide E (2) and their analogues was evaluated. We found that (-)-euphopilolide (1) and (-)-jolkinolide E (2) inhibited the proliferation and induced apoptosis in HCC cells. These findings lay a good foundation for further pharmacology studies of abietane lactone derivatives and provide valuable insight for the development of anti-HCC small molecule drug of natural product origin.
RESUMEN
Myocardial infarction (MI) is a cardiovascular emergency and the leading cause of death worldwide. Inflammatory and immune responses are initiated immediately after MI, leading to myocardial death, scarring, and ventricular remodeling. Current therapeutic approaches emphasize early restoration of ischemic myocardial reperfusion, but there is no effective treatment for the pathological changes of infarction. Biomedical materials development has brought new hope for MI diagnosis and treatment. Biomedical materials, such as cardiac patches, hydrogels, nano biomaterials, and artificial blood vessels, have played an irreplaceable role in MI diagnosis and treatment. They improve the accuracy and efficacy of MI diagnosis and offer further possibilities for reducing inflammation, immunomodulation, inhibiting fibrosis, and cardiac regeneration. This review focuses on the advances in biomedical materials applications in MI diagnosis and treatment. The current studies are outlined in terms of mechanisms of action and effects. It is addressed how biomedical materials application can lessen myocardial damage, encourage angiogenesis, and enhance heart function. Their clinical transformation value and application prospect are discussed.
Asunto(s)
Infarto del Miocardio , Humanos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Corazón , Miocardio , Materiales Biocompatibles , HidrogelesRESUMEN
Limited studies have examined the associations between diet quality and gestational weight gain (GWG) among Chinese pregnant women, adopting Chinese GWG guidelines. We prospectively investigate the associations of diet quality, using the Chinese Healthy Diet Index for Pregnancy (CHDI-P), which assessed diet quality from 'Diversity', 'Adequacy' and 'Limitation' dimensions with overall 100 points, with GWG among participants enroled in Southwest China. Food consumption was collected by 24 h dietary recalls for three consecutive days and CHDI-P scores were divided into tertiles. GWG was calculated according to the weight measured before delivery and classified into adequate weight gain (AWG), insufficient weight gain (IWG) and excessive weight gain(EWG) following Chinese GWG guidelines. Multinomial regression analyses and stratified analyses by pre-pregnancy body mass index were performed to estimate the association between CHDI-P and GWG. A total of 1416 participants were recruited in early pregnancy, and 971 and 997 participants were respectively followed up in middle and late pregnancy. The mean CHDI-P score was 56.44 ± 6.74, 57.07 ± 7.44 and 57.38 ± 7.94 points in early, middle and late pregnancy, respectively. Women in the lowest CHDI-P scores group had an increased risk of EWG in middle (OR = 1.53, 95% confidence interval [CI] = 1.08-2.17) and late pregnancy (OR = 1.71, 95% CI = 1.21-2.41) than women in the highest group, while overweight/obese women had a greater risk of EWG in late pregnancy (OR = 4.25, 95% CI = 1.30-13.90). No association was found between the CHDI-P scores and IWG. Poor diet quality in middle and late pregnancy was associated with a higher risk of EWG.
Asunto(s)
Ganancia de Peso Gestacional , Embarazo , Femenino , Humanos , Dieta Saludable , Estudios Prospectivos , Pueblos del Este de Asia , Aumento de Peso , Dieta/efectos adversos , Índice de Masa CorporalRESUMEN
OBJECTIVE: Investigate and evaluate the levels and sources of calcium intake of pregnant women in Chengdu during three trimesters. METHODS: Use the data of a cohort study in Chengdu in 2017. The healthy singleton pregnant women with 8-14 weeks of pregnancy in an obstetrical clinic of a maternal-and-child health care institution in Chengdu were selected as the object of the study. Data on maternal demographic characteristics and the use information of calcium supplements in the past month of each trimester were collected by questionnaire investigation. The dietary intakes data of pregnant women in each trimester was collected by the 3-day 24-hour dietary recall method. The dietary calcium intake and the contribution of calcium from different foods were calculated based on the Chinese Food Composition Table(2018). The total calcium intake was obtained by adding the dietary calcium and supplement calcium intake. The calcium intake was evaluated with reference to the Chinese Dietary Nutrient Reference Intakes(2013). RESULTS: Valid samples of 1653 cases in early pregnancy, 1024 cases in middle pregnancy and 1017 cases in late pregnancy were finally included. The median intake of total calcium was 523.3, 1280.5 and 1491.3 mg/d in three trimesters, respectively. The adequate rate of total calcium intake was 16.3%, 63.2% and 67.1%, the insufficient rate was 69.0%, 15.7% and 11.2%, the excess rate was 0.2%, 9.1% and 14.4%, respectively. The median intake of dietary calcium was 453.0, 613.0 and 723.0 mg/d in three trimesters respectively. The dietary calcium adequate rates were 7.1%, 9.7% and 16.2%, the dietary calcium deficiency rates were 82.0%, 75.0%, 62.6%, respectively. The main food sources of dietary calcium in each pregnancy were dairy foods, vegetables, tubers and grains. The contribution of dairy foods to the dietary calcium was 33.8%, 37.7% and 40.2%, respectively. The median intake of milk was 125.0, 235.3 and 250.0 g/d, respectively. Among all pregnant women, the calcium supplement use in three trimesters was 36.2%, 93.4% and 91.7%, respectively; the median intake of supplement calcium was 0.0, 625.0 and 750.0 mg/d, respectively. Among pregnant women who met the dietary calcium standard, the use of calcium supplements in the three trimesters was 38.1%, 95.0% and 94.5%, respectively; the median intake of supplemental calcium was 0.0, 725.0 and 750.0 mg/d, respectively. CONCLUSION: The insufficient and excessive total calcium intake coexisted among pregnant women in Chengdu, with the insufficient dietary calcium intake prominent in all trimesters. The use of calcium supplements was common in middle and late pregnancy.
Asunto(s)
Calcio , Mujeres Embarazadas , Embarazo , Femenino , Humanos , Calcio de la Dieta , Estudios de Cohortes , Dieta , Suplementos Dietéticos , HospitalesRESUMEN
In vitro experiments have indicated prebiotic activity of isomaltulose, which stimulates the growth of probiotics and the production of short chain fatty acids (SCFAs). However, the absence of in vivo trials undermines these results. This study aims to investigate the effect of isomaltulose on composition and functionality of gut microbiota in rats. Twelve Sprague-Dawley rats were divided into two groups: the IsoMTL group was given free access to water containing 10% isomaltulose (w/w), and the control group was treated with normal water for five weeks. Moreover, 16S rRNA sequencing showed that ingestion of isomaltulose increased the abundances of beneficial microbiota, such as Faecalibacterium and Phascolarctobacterium, and decreased levels of pathogens, including Shuttleworthia. Bacterial functional prediction showed that isomaltulose affected gut microbial functionalities, including secondary bile acid biosynthesis. Targeted metabolomics demonstrated that isomaltulose supplementation enhanced cholic acid concentration, and reduced levels of lithocholic acid, deoxycholic acid, dehydrocholic acid, and hyodeoxycholic acid. Moreover, the concentrations of propionate and butyrate were elevated in the rats administered with isomaltulose. This work suggests that isomaltulose modulates gut microbiota and the production of SCFAs and secondary bile acids in rats, which provides a scientific basis on the use of isomaltulose as a prebiotic.
Asunto(s)
Ácidos y Sales Biliares/metabolismo , Ácidos Grasos Volátiles/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Isomaltosa/análogos & derivados , Probióticos/farmacología , Animales , Prueba de Tolerancia a la Glucosa , Isomaltosa/farmacología , Masculino , ARN Ribosómico 16S/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Transthoracic echocardiography is routinely performed in patients with stroke or transient ischemic attack (TIA) to help plan secondary stroke management, but recent data evaluating its usefulness in this context are lacking. We sought to evaluate the value of echocardiography for identifying clinically actionable findings for secondary stroke prevention. METHODS: We conducted a multicentre cohort study of patients admitted to hospital with stroke or TIA between 2010 and 2015 at 2 academic hospitals in Toronto, Ontario, Canada. Clinically actionable echocardiographic findings for secondary stroke prevention included cardiac thrombus, patent foramen ovale, atrial myxoma or valvular vegetation. We identified patient characteristics associated with clinically actionable findings using logistic regression. RESULTS: Of the 1862 patients with stroke or TIA we identified, 1272 (68%) had at least 1 echocardiogram. Nearly all echocardiograms were transthoracic; 1097 (86%) were normal, 1 (0.08%) had an atrial myxoma, 2 (0.2%) had a valvular vegetation, 11 (0.9%) had a cardiac thrombus and 66 (5.2%) had a PFO. Patent foramen ovale was less likely among patients older than 60 years (adjusted odds ratio [OR] 0.34, 95% confidence interval [CI] 0.20-0.57), with prior stroke or TIA (adjusted OR 0.31, 95% CI 0.09-0.76) or with dyslipidemia (adjusted OR 0.39, 95% CI 0.15-0.84). Among the 130 patients with cryptogenic stroke who had an echocardiogram (n = 110), a PFO was detected in 19 (17%) on transthoracic echocardiogram. INTERPRETATION: Most patients with stroke or TIA had a normal echocardiogram, with few having clinically actionable findings for secondary stroke prevention. Clinically actionable findings, specifically PFO, were more common in patients with cryptogenic stroke.
Asunto(s)
Ecocardiografía Transesofágica , Ventrículos Cardíacos/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Estudios de Cohortes , Femenino , Foramen Oval Permeable/diagnóstico por imagen , Humanos , Ataque Isquémico Transitorio/diagnóstico por imagen , Masculino , Persona de Mediana Edad , OntarioRESUMEN
BACKGROUND: Understanding the most common and costly conditions treated by inpatient general medical services is important for implementing quality improvement, developing health policy, conducting research, and designing medical education. OBJECTIVE: To determine the prevalence and cost of conditions treated on general internal medicine (GIM) inpatient services. DESIGN: Retrospective cross-sectional study involving 7 hospital sites in Toronto, Canada. PARTICIPANTS: All patients discharged between April 1, 2010 and March 31, 2015 who were admitted to or discharged from an inpatient GIM service. MAIN MEASURES: Hospital administrative data were used to identify diagnoses and costs associated with admissions. The primary discharge diagnosis was identified for each admission and categorized into clinically relevant and mutually exclusive categories using the Clinical Classifications Software (CCS) tool. KEY RESULTS: Among 148,442 admissions, the most common primary discharge diagnoses were heart failure (5.1%), pneumonia (5.0%), urinary tract infection (4.6%), chronic obstructive pulmonary disease (4.5%), and stroke (4.4%). The prevalence of the 20 most common conditions was significantly correlated across hospitals (correlation coefficients ranging from 0.55 to 0.95, p ≤ 0.01 for all comparisons). No single condition represented more than 5.1% of all admissions or more than 7.9% of admissions at any hospital site. The costliest conditions were stroke (median cost $7122, interquartile range 5587-12,354, total cost $94,199,422, representing 6.0% of all costs) and the group of delirium, dementia, and cognitive disorders (median cost $12,831, IQR 9539-17,509, total cost $77,372,541, representing 4.9% of all costs). The 10 most common conditions accounted for only 36.2% of hospitalizations and 36.8% of total costs. The remaining hospitalizations included 223 different CCS conditions. CONCLUSIONS: GIM services care for a markedly heterogeneous population but the most common conditions were similar across 7 hospitals. The diversity of conditions cared for in GIM may be challenging for healthcare delivery and quality improvement. Initiatives that cut across individual diseases to address processes of care, patient experience, and functional outcomes may be more relevant to a greater proportion of the GIM population than disease-specific efforts.
Asunto(s)
Medicina General/economía , Costos de la Atención en Salud , Hospitalización/economía , Medicina Interna/economía , Alta del Paciente/economía , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Medicina General/tendencias , Costos de la Atención en Salud/tendencias , Hospitalización/tendencias , Humanos , Medicina Interna/tendencias , Masculino , Persona de Mediana Edad , Alta del Paciente/tendencias , Prevalencia , Estudios RetrospectivosRESUMEN
Neoatherosclerosis (NA) within stents has become an important clinical problem after coronary artery stent implantation. In-stent restenosis and in-stent thrombosis are the two major complications following coronary stent placement and seriously affect patient prognosis. As the common pathological basis of these two complications, NA plaques, unlike native atherosclerotic plaques, often grow around residual oxidized lipids and stent struts. The main components are foam cells formed by vascular smooth muscle cells (VSMCs) engulfing oxidized lipids at lipid residue sites. Current research mainly focuses on optical coherence tomography (OCT) and intravascular ultrasound (IVUS), but the specific pathogenesis of NA is still unclear. A thorough understanding of the pathogenesis and pathological features of NA provides a theoretical basis for clinical treatment. This article reviews the previous research of our research group and the current situation of domestic and foreign research.
Asunto(s)
Tomografía de Coherencia Óptica , Humanos , Reestenosis Coronaria/etiología , Reestenosis Coronaria/diagnóstico por imagen , Reestenosis Coronaria/terapia , Reestenosis Coronaria/patología , Aterosclerosis/terapia , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/metabolismo , Aterosclerosis/patología , Placa Aterosclerótica/patología , Placa Aterosclerótica/terapia , Placa Aterosclerótica/diagnóstico por imagen , Stents/efectos adversos , Músculo Liso Vascular/patología , Músculo Liso Vascular/metabolismo , Ultrasonografía Intervencional/métodos , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/patología , Células Espumosas/patología , Células Espumosas/metabolismo , Miocitos del Músculo Liso/patología , Miocitos del Músculo Liso/metabolismoRESUMEN
BACKGROUND: Chemotaxis and trafficking of dendritic cells (DCs) induced by cytokine receptors are crucial steps in rheumatoid arthritis (RA) pathogenesis. C-C chemokine receptor type 5 (CCR5) plays a key role in DC movement and has been implicated in multitudinous inflammatory and immunology diseases. Thus, targeting CCR5 to suppress DC chemotaxis is considered as a potential strategy for the management of RA. METHODS: Herein, we first synthesized a new hybrid named CT3-1 which based on artesunate and isatin. Besides, we studied the regulating effectiveness of CT3-1 on bone marrow-derived DCs (BMDCs) and on collagen-induced arthritis (CIA) through RNA-seq analysis, cell function experiments in vitro and mice model in vivo. RESULTS: The results shown that CT3-1 mainly reduced CCR5 expression of immature BMDCs and importantly inhibited immature BMDC migration induced by CCR5 in vitro, with no or minor influence on other functions of DCs, such as phagocytosis and maturation. In the mouse model, CT3-1 relieved arthritis severity and inhibited CIA development. Furthermore, CT3-1 intervention decreased the expression of CCR5 in DCs and reduced the proportion of DCs in the peripheral blood of CIA mice. CONCLUSIONS: Our findings suggest that CCR5-induced chemotaxis and trafficking of immature DCs are important in RA. Targeting CCR5 and inhibiting immature DC chemotaxis may provide a novel choice for the treatment of RA and other similar autoimmune diseases. Moreover, we synthesized a new hybrid compound CT3-1 that could inhibit immature DC trafficking and effectively relieve RA by directly reducing the CCR5 expression of immature DCs.
Asunto(s)
Artesunato , Artritis Experimental , Artritis Reumatoide , Quimiotaxis , Células Dendríticas , Receptores CCR5 , Animales , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Receptores CCR5/metabolismo , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/inmunología , Quimiotaxis/efectos de los fármacos , Artesunato/farmacología , Artesunato/uso terapéutico , Ratones , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Ratones Endogámicos DBA , Masculino , Células Cultivadas , HumanosRESUMEN
Due to the cardiotoxicity of doxorubicin (DOX), its clinical application is limited. Lipid peroxidation caused by excessive ferrous iron is believed to be a key molecular mechanism of DOX-induced cardiomyopathy (DIC). Dexrazoxane (DXZ), an iron chelator, is the only drug approved by the FDA for reducing DIC, but it has many side effects and cannot be used as a preventive drug in clinical practice. Single-nucleus RNA sequencing (snRNA-seq) analysis identified myocardial and epithelial cells that are susceptible to DOX-induced ferroptosis. The glutathione peroxidase 4 (GPX4) activator selenomethione (SeMet) significantly reduced polyunsaturated fatty acids (PUFAs) and oxidized lipid levels in vitro. Consistently, SeMet significantly decreased DOX-induced lipid peroxidation in H9C2 cells and mortality in C57BL/6 mice compared to DXZ, ferrostatin-1, and normal saline. SeMet can effectively reduce serum markers of cardiac injury in C57BL/6 mice and breast cancer patients. Depletion of the GPX4 gene in C57BL/6 mice resulted in an increase in polyunsaturated fatty acid (PUFA) levels and eliminated the protective effect of SeMet against DIC. Notably, SeMet exerted antitumor effects on breast cancer models with DOX while providing cardiac protection for the same animal without detectable toxicities. These findings suggest that pharmacological activation of GPX4 is a valuable and promising strategy for preventing the cardiotoxicity of doxorubicin.
Asunto(s)
Neoplasias de la Mama , Cardiomiopatías , Humanos , Ratones , Animales , Femenino , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Cardiotoxicidad/etiología , Ratones Endogámicos C57BL , Cardiomiopatías/inducido químicamente , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/patología , Doxorrubicina/efectos adversos , Ácidos Grasos InsaturadosRESUMEN
BACKGROUND: Reducing laboratory test overuse is important for high quality, patient-centred care. Identifying priorities to reduce low value testing remains a challenge. OBJECTIVE: To develop a simple, data-driven approach to identify potential sources of laboratory overuse by combining the total cost, proportion of abnormal results and physician-level variation in use of laboratory tests. DESIGN, SETTING AND PARTICIPANTS: A multicentre, retrospective study at three academic hospitals in Toronto, Canada. All general internal medicine (GIM) hospitalisations between 1 April 2010 and 31 October 2017. RESULTS: There were 106 813 GIM hospitalisations during the study period, with median hospital length-of-stay of 4.6 days (IQR: 2.33-9.19). There were 21 tests which had a cumulative cost >US$15 400 at all three sites. The costliest test was plasma electrolytes (US$4 907 775), the test with the lowest proportion of abnormal results was red cell folate (0.2%) and the test with the greatest physician-level variation in use was antiphospholipid antibodies (coefficient of variation 3.08). The five tests with the highest cumulative rank based on greatest cost, lowest proportion of abnormal results and highest physician-level variation were: (1) lactate, (2) antiphospholipid antibodies, (3) magnesium, (4) troponin and (5) partial thromboplastin time. In addition, this method identified unique tests that may be a potential source of laboratory overuse at each hospital. CONCLUSIONS: A simple multidimensional, data-driven approach combining cost, proportion of abnormal results and physician-level variation can inform interventions to reduce laboratory test overuse. Reducing low value laboratory testing is important to promote high value, patient-centred care.
Asunto(s)
Pacientes Internos , Médicos , Humanos , Estudios Retrospectivos , Hospitalización , Medicina InternaRESUMEN
Carbon emission trading has been actively applied in many countries, and its operational effect has received widespread attention. However, previous studies mostly focused on single environmental effect, and the investigation of the comprehensive environmental effect needs to be further supplemented. Based on this, this paper explores the comprehensive environmental effect of carbon emission trading with eco-efficiency as the starting point. First, this paper measures eco-efficiency using the super-efficient minimum distance to strong efficient frontier (MinDS) model with undesirable outputs. Second, this paper uses the propensity score matching difference in difference (PSM-DID) model to quantify the effect of carbon emission trading on eco-efficiency. Finally, this paper examines the mediating mechanism of the effect of carbon emission trading on eco-efficiency based on the mediating effect model. The results show that carbon emission trading can improve the level of urban eco-efficiency. Energy savings and increased efficiency effectively mediate the promoting effect of carbon emission trading on eco-efficiency. The mediating push effect of R&D innovation and industrial structure restructuring has not yet appeared. This paper can not only provide policy basis for the improvement of carbon emission trading market but also provide reference for the construction of carbon emission trading market in developing countries.
Asunto(s)
Carbono , Gases de Efecto Invernadero , Carbono/análisis , Industrias , Eficiencia , ChinaRESUMEN
Aim: The destruction of the vascular endothelial barrier mediated by Ox-LDL is the initial link to atherosclerosis. Here, we aimed to determine whether the immunological intervention with Ox-ApoB polypeptide fragment (Ox-ApoB-PF) can block the deposition of Ox-LDL in vascular endothelial cells through LOX-1 receptors, thereby protecting the barrier function and survival status of vascular endothelial cells and inhibiting the progression of atherosclerosis. Methods and Results: In order to determine the harm of Ox-LDL to vascular endothelial cells and the protective effect of immune intervention with Ox-ApoB-PF, we conducted a series of corresponding experiments in vitro and in vivo. The in vitro results showed that Ox-LDL can activate endothelial cell apoptosis pathway; reduce the expression of endothelial junction proteins; affect the migration, deformation, and forming ability; and ultimately destroy the vascular endothelial barrier function. The increased permeability of endothelial cells led to a sharp increase in the phagocytosis of Ox-LDL by macrophages under the endothelial layer. Meanwhile, Ox-LDL stimulation induced a significant upregulation of LOX-1 in endothelial cells and increased the expression of endothelial cell chemokines and adhesion factors. Ox-ApoB-PF antibodies can significantly reduce the abovementioned harmful effects. The in vivo results showed that active immune intervention through Ox-ApoB-PF can protect the endothelial barrier function; reduce macrophage deposition and the inflammatory response in plaques; alleviate lipid deposition in the plaques, as well as apoptosis and necrosis; and increase the ability of liver macrophages to clear Ox-LDL. Eventually, the progression of plaque and the formation of necrotic cores in plaques can be inhibited. Conclusions: An Ox-ApoB-PF antibody may protect the endothelial cell physiological function and survival status by blocking the combination of Ox-LDL/LOX-1 in vascular endothelial cells. Immune intervention with Ox-ApoB-PF inhibits the occurrence and development of atherosclerotic lesions by protecting the vascular endothelial barrier function.
Asunto(s)
Aterosclerosis , Placa Aterosclerótica , Apolipoproteínas B/farmacología , Aterosclerosis/patología , Células Endoteliales/metabolismo , Humanos , Lipoproteínas LDL/metabolismo , Receptores Depuradores de Clase E/metabolismoRESUMEN
Given the context of the global energy shortage and the deterioration of the ecological environment, this paper uses industrial linkage as a starting point to deeply explore the energy consumption of different sectors and its transfer characteristics. First, a dual evaluation of energy consumption in various sectors is conducted from the perspectives of production and demand to realize an integrated analysis from the energy consumption perspective. Second, based on industrial linkage, the economic input-output life cycle assessment (EIO-LCA) model is used to quantify the net transfer of energy consumption and identify the transfer of energy consumption pressure embodied in economic activities by various sectors. Finally, the energy consumption of various sectors is decomposed, and the transfer flow of energy consumption is measured to accurately quantify the degree of linkage in the energy consumption of sectors. The results show that the current direct energy consumption intensity of various sectors in China is continuously decreasing, but this decrease is insufficient to reverse the upward trend in energy consumption demand. From the perspective of production and demand, non-energy industrial sector is a key sector for reducing energy consumption, and the intersectoral linkage between the subsectors caused by product trade flows has a greater impact on the level of direct and embodied energy consumption. Direct and embodied energy consumption in the same sector can be ranked quite differently, and their levels may not be equal. Energy sector is the main net outflow sector of energy consumption, and the level of its direct energy consumption is much higher than that of its embodied energy consumption. It is worth noting that the scale of embodied energy consumption in construction industry is much higher than the scale of direct energy consumption. Construction is the sector with the greatest net inflow of energy consumed and is the main driver of the energy consumption transfer of energy sector and non-energy industrial sector.
Asunto(s)
Desarrollo Económico , Industrias , ChinaRESUMEN
OBJECTIVE: The aim of this study was to investigate the potential therapeutic effects of a newly discovered osteopontin-derived synthetic peptide "RSKKFRR" in a rat model of ischemic stroke. METHODS: A total of 24 male SD rats were randomly divided into three groups. The model of ischemic stroke was made up of the middle cerebral artery occlusion (MACO). The rats were divided into sham operation group (Sham), control group (MACO + PBS) and treatment group (MACO + OPNpt9), eight rats in each group. In the control group and the treatment group, PBS or OPNpt9 was injected into the nasal cavity after MACO once a day, and the area of new blood vessels and the recovery of nerve function were observed 14 days later. Whether the proliferation, migration and tube formation of HUVECs were promoted by OPNpt9 was tested. The expression levels of related proangiogenic factors were also detected. RESULTS: OPNpt9 was found to contribute to cerebral microvascular remodeling and neurological improvement in ischemic rats while promoting endothelial cell migration, proliferation and tube formation in vitro. These effects were mediated by activation of the p-ERK/MMP-9/VEGF pathway. CONCLUSION: In conclusion, OPNpt9 promotes angiogenesis and neurological recovery after ischemic stroke.