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BACKGROUND: Enantiodiscrimination of chiral drugs is critical for understanding physiological phenomena and ensuring medical safety. Although enantiomers of these drugs share identical physicochemical properties, they exhibit significant differences in pharmacodynamic, pharmacokinetic, and toxicological properties due to the differences in their three-dimensional shapes. Therefore, the development of effective methods for chiral recognition is of great significance and has been a hot topic in chemo/biological studies. RESULTS: In this study, we designed a recognition receptor comprising a α-hemolysin (α-HL) nanopore and sulfobutyl ether-ß-cyclodextrin (SBEßCD) for identifying the enantiomers of the antidepressant duloxetine at the single-molecule level. Chiral molecules were discriminated based on the different current blockages within the recognition receptor. The results indicated a strong interaction between R-duloxetine and the recognition receptor. By combining the experimental data and molecular docking results, we explored the recognition mechanism of the designed nanopore recognition receptor for chiral drug molecules. It was found that hydrophobic and electrostatic interactions play key roles in chiral recognition. Additionally, by comparing the binding kinetics of enantiomers to cyclodextrins in confined nanospace and bulk solution, we found that enantiomeric identification was better facilitated in the confined nanospace. Finally, the enantiomeric excess (ee) of the enantiomeric duloxetine mixture was measured using this recognized receptor. SIGNIFICANCE: This strategy has the advantages of low cost, high sensitivity, and no need for additional derivative modifications, providing a new perspective on the development of chiral recognition sensors with excellent enantioselectivity in drug design, pharmaceuticals, and biological applications.
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Clorhidrato de Duloxetina , Simulación del Acoplamiento Molecular , Nanoporos , Estereoisomerismo , Clorhidrato de Duloxetina/química , Clorhidrato de Duloxetina/metabolismo , Clorhidrato de Duloxetina/farmacología , beta-Ciclodextrinas/químicaRESUMEN
BACKGROUND: Numerous gene signatures predicting the prognosis of bladder cancer have been identified. However, a tumor-specific T cell signature related to immunotherapy response in bladder cancer remains under investigation. METHODS: Single-cell RNA and TCR sequencing from the Gene expression omnibus (GEO) database were used to identify tumor-specific T cell-related genes in bladder cancer. Subsequently, we constructed a tumor-specific T cell signature (TstcSig) and validated its clinical relevance for predicting immunotherapy response in multiple immunotherapy cohorts. Further analyses explored the immune characteristics of TstcSig in bladder cancer patients from other cohorts in the TCGA and GEO databases. Western blot (WB), multicolor immunofluorescence (MIF), qRT-PCR and flow cytometry assays were performed to validate the results of bioinformatics analysis. RESULTS: The established TstcSig, based on five tumor-specific T cell-related genes, could predict outcomes in a bladder cancer immunotherapy cohort. This was verified using two additional immunotherapy cohorts and showed better predictive performance compared to 109 published T cell signatures. TstcSig was strongly correlated with immune characteristics such as immune checkpoint gene expression, tumor mutation burden, and T cell infiltration, as validated by single-cell and spatial transcriptomics datasets. Notably, the positive correlation between TstcSig and T cell infiltration was confirmed in the TCGA cohort. Furthermore, pan-cancer analysis demonstrated the heterogeneity of the prognostic value of TstcSig. Tumor-specific T cells highly expressed CD27, IFNG, GZMB and CXCL13 and secreted more effector cytokines for tumor cell killing, as validated experimentally. CONCLUSION: We developed a five-gene signature (including VAMP5, TIGIT, LCK, CD27 and CACYBP) based on tumor-specific T cell-related genes to predict the immunotherapy response in bladder cancer patients.
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AIMS: This study aimed to investigate the association between dietary protein intake and mortality among patients with diabetic kidney disease. METHODS: The research encompassed a total of 2901 participants diagnosed with diabetic kidney disease, drawn from the National Health and Nutrition Examination Survey (NHANES). To determine outcomes related to all-cause and cardiovascular mortality, connections were established with the National Death Index up until December 31, 2019. Estimations of hazard ratios (HRs) and their corresponding 95 % confidence intervals (CIs) were conducted using Cox proportional hazard ratio models. RESULTS: During the 261,239 person-years of follow-up, 1236 deaths were recorded. After multivariate adjustment, the weighted hazard ratio (HR) and 95 % CIs for participants with 1.0-1.2 g/kg of protein intake was 0.65 (0.44, 0.96) for all-cause mortality. A higher proportion of animal protein intake was found to be associated with an increased mortality risk. Stratified analyses showed that higher protein intake benefited older participants. CONCLUSIONS: In diabetic kidney disease patients, 1.0-1.2 g/kg of protein was associated with lower mortality and 0.6-1.2 g/kg of protein especially benefitted patients ≥60 years.
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The i-motif, a secondary structure of a four-helix formed by cytosine-rich DNA (i-DNA) through C-C+ base pairing, is prevalent in human telomeres and promoters. This structure creates steric hindrance, thereby inhibiting both gene expression and protein coding. The conformation of i-DNA is intricately linked to the intracellular ionic environment. Hence, investigating its conformation under various ion conditions holds significant importance. In this study, we explored the impact of cations on the i-motif structure at the single-molecule level using the α-hemolysin (α-HL) nanochannel. Our findings reveal that the ability of i-DNA to fold into the i-motif structure follows the order Cs+ > Na+ > K+ > Li+ for monovalent cations. Furthermore, we observed the interconversion of single-stranded DNA (ss-DNA) and the i-motif structure at high and low concentrations of Mg2+ and Ba2+ electrolyte solutions. This study not only has the potential to extend the application of i-motif-based sensors in complex solution environments but also provides a new idea for the detection of metal ions.
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Cationes , ADN , Proteínas Hemolisinas , Nanoporos , ADN/química , Cationes/química , Proteínas Hemolisinas/química , Conformación de Ácido Nucleico , Motivos de Nucleótidos , Citosina/química , ADN de Cadena Simple/químicaRESUMEN
Background: The treatment of multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) remains challenging due to the limited availability of effective drugs. Linezolid has emerged as a promising therapeutic option for these cases. However, its long-term use can lead to complications such as peripheral and optic neuropathies. Acupuncture, a cornerstone of traditional Chinese medicine, has been shown to be effective in the treatment of peripheral neuropathy (PN). This study examines the potential benefits of acupuncture in the treatment of linezolid-induced peripheral neuropathy (LIPN). Methods: Four patients, aged 27 to 60 years, diagnosed with LIPN, underwent daily acupuncture treatments. The main endpoint was to assess the efficacy of acupuncture in reducing neuropathic pain associated with LIPN in patients. This was primarily measured using changes in the Short Form McGill Pain Questionnaire (SF-MPQ) scores before and after acupuncture treatment. Results: Three of the patients experienced significant symptom remission, while one experienced marginal improvement. Treatments ranged from 7 to 18 sessions. Specifically, the first patient reported substantial relief with a score reduction from 33 to 13; the second patient observed minimal change; the third patient's score decreased dramatically from 10 to 2 after eight sessions; the last patient had a score reduction from 21 to 12 after five sessions, but did not continue treatment for a second assessment. Conclusion: Acupuncture is a promising therapeutic approach for LIPN. However, larger and more thorough studies are needed to determine its full potential.
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PURPOSE: The current study investigated the correlation between dietary iron intake and diabetic kidney disease among diabetic adults. METHODS: This cross-sectional study enrolled 8118 participants who suffered from diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Dietary iron intake was obtained from 24 h recall interviews, and diabetic kidney disease was defined as eGFR < 60 mL/min per 1.73 m2 or albumin creatinine ratio (ACR) ≥ 30 mg/g. Three weighted logistic regression models were utilized to investigate odd ratio (OR) and 95% CIs for diabetic kidney disease. Stratified analyses were performed by gender, age, BMI, HbA1c, hypertension status, and smoking status, and diabetes types. RESULTS: Among 8118 participants (51.6% male, mean age 61.3 years), 40.7% of participants suffered from diabetic kidney disease. With the adjustment of potential covariates, we found that ≥ 12.59 mg of dietary iron was related to a lower risk of diabetic kidney disease (OR = 0.78, 95% CI: 0.63 to 0.96; OR = 0.79, 95% CI: 0.63 to 0.98). In stratified analyses, higher iron intake was negatively related to diabetic kidney disease, especially among those who were male, < 60 years, those with hypertension, those with HbA1c < 7.0%, and those who were ex-smokers. The result remained robust in sensitivity analyses. CONCLUSION: We found that ≥ 12.59 mg of dietary iron is associated with a lower risk of diabetic kidney disease, especially in those who were male, younger, heavier weight, have better blood sugar control, and those who were ex-smokers.
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Nefropatías Diabéticas , Hierro de la Dieta , Encuestas Nutricionales , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Nefropatías Diabéticas/epidemiología , Anciano , Hierro de la Dieta/administración & dosificación , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Adulto , Factores de RiesgoRESUMEN
BACKGROUND AND PURPOSE: Accelerating the image acquisition speed of MR imaging without compromising the image quality is challenging. This study aimed to evaluate the feasibility of contrast-enhanced (CE) 3D T1WI and CE 3D-FLAIR sequences reconstructed with compressed sensitivity encoding artificial intelligence (CS-AI) for detecting brain metastases (BM) and explore the optimal acceleration factor (AF) for clinical BM imaging. MATERIALS AND METHODS: Fifty-one patients with cancer with suspected BM were included. Fifty participants underwent different customized CE 3D-T1WI or CE 3D-FLAIR sequence scans. Compressed SENSE encoding acceleration 6 (CS6), a commercially available standard sequence, was used as the reference standard. Quantitative and qualitative methods were used to evaluate image quality. The SNR and contrast-to-noise ratio (CNR) were calculated, and qualitative evaluations were independently conducted by 2 neuroradiologists. After exploring the optimal AF, sample images were obtained from 1 patient by using both optimized sequences. RESULTS: Quantitatively, the CNR of the CS-AI protocol for CE 3D-T1WI and CE 3D-FLAIR sequences was superior to that of the CS protocol under the same AF (P < .05). Compared with reference CS6, the CS-AI groups had higher CNR values (all P < .05), with the CS-AI10 scan having the highest value. The SNR of the CS-AI group was better than that of the reference for both CE 3D-T1WI and CE 3D-FLAIR sequences (all P < .05). Qualitatively, the CS-AI protocol produced higher image quality scores than did the CS protocol with the same AF (all P < .05). In contrast to the reference CS6, the CS-AI group showed good image quality scores until an AF of up to 10 (all P < .05). The CS-AI10 scan provided the optimal images, improving the delineation of normal gray-white matter boundaries and lesion areas (P < .05). Compared with the reference, CS-AI10 showed reductions in scan time of 39.25% and 39.93% for CE 3D-T1WI and CE 3D-FLAIR sequences, respectively. CONCLUSIONS: CE 3D-T1WI and CE 3D-FLAIR sequences reconstructed with CS-AI for the detection of BM may provide a more effective alternative reconstruction approach than CS. CS-AI10 is suitable for clinical applications, providing optimal image quality and a shortened scan time.
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Neoplasias Encefálicas , Sustancia Blanca , Humanos , Inteligencia Artificial , Neoplasias Encefálicas/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Sustancia Gris , Imagenología TridimensionalRESUMEN
Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, for the scratch wound assay experiments shown in Fig. 1 on p. 2413, the panels showing the '0 h' experiments for the respective incubations with VEGF or BC001 were apparently identical. The authors were able to reexamine their original data files, and realized that this figure had been inadverently assembled incorrectly. The revised version of Fig. 1, containing the correct data for the '0 h / BC001' panel, is shown below. Note that the revisions made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [International Journal of Oncology 45: 24112420, 2014; DOI: 10.3892/ijo.2014.2690].
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In order to ensure the safe operation of buried polyethylene pipelines adjacent to blasting excavations, controlling the effects of blasting vibration loads on the pipelines is a key concern. Model tests on buried polyethylene pipelines under blasting loads were designed and implemented, the vibration velocity and dynamic strain response of the pipelines were obtained using a TC-4850 blast vibrometer and a UT-3408 dynamic strain tester, and the distribution characteristics of blast vibration velocity and dynamic strain were analyzed based on the experimental data. The results show that the blast load has the greatest effect on the circumferential strain of the polyethylene pipe, and the dynamic strain response is greatest at the section of the pipe nearest to the blast source. Pipe peak vibration velocity (PPVV), ground peak particle velocity (GPPV), and the peak dynamic strain of the pipe were highly positively correlated, which verifies the feasibility of using GPPV to characterize pipeline vibration and strain level. According to the failure criteria and relevant codes, combined with the analysis of experimental results, the safety threshold of additional circumferential stress on the pipeline is 1.52 MPa, and the safety control vibration speed of the ground surface is 21.6 cm/s.
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Developing cost-effective and highly efficient photocathodes toward polysulfide redox reduction is highly desirable for advanced quantum dot (QD) photovoltaics. Herein, we demonstrate nitrogen doped carbon (N-C) shell-supported iron single atom catalysts (Fe-SACs) capable of catalyzing polysulfide reduction in QD photovoltaics for the first time. Specifically, Fe-SACs with FeN4 active sites feature a power conversion efficiency of 13.7% for ZnCuInSe-QD photovoltaics (AM1.5G, 100 mW/cm2), which is the highest value for ZnCuInSe QD-based photovoltaics, outperforming those of Cu-SACs and N-C catalysts. Compared with N-C, Fe-SACs exhibit suitable energy level matching with polysulfide redox couples, revealed by the Kelvin probe force microscope, which accelerates the charge transferring at the interfaces of catalyst/polysulfide redox couple. Density functional theory calculations demonstrate that the outstanding catalytic activity of Fe-SACs originates from the preferable adsorption of S42- on the FeN4 active sites and the high activation degree of the S-S bonds in S42- initiated by the FeN4 active sites.
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PURPOSE: Shorter courses of breast radiotherapy are offered as an alternative to 4 weeks of whole-breast irradiation after lumpectomy, including brachytherapy. A prospective phase 2multi-institution clinical trial to study 3-fraction accelerated partial breast irradiation delivered by brachytherapy was conducted. METHODS AND MATERIALS: The trial treated selected breast cancers after breast-conserving surgery with brachytherapy applicators that delivered 22.5 Gy in 3 fractions of 7.5 Gy. The planning treatment volume was 1 to 2 cm beyond the surgical cavity. Eligible women were age ≥45 years with unicentric invasive or in situ tumors ≤3 cm excised with negative margins and with positive estrogen or progesterone receptors and no metastases to axillary nodes. Strict dosimetric parameters were required to be met and follow up information was collected from the participating sites. RESULTS: Two hundred patients were prospectively enrolled; however, a total of 185 patients who were enrolled were followed for a median of 3.63 years. Three-fraction brachytherapy was associated with low chronic toxicity. There was excellent or good cosmesis in 94% of patients. There were no grade 4 toxicities. Grade 3 fibrosis at the treatment site was present in 1.7% and 32% percent had grades 1 or 2 fibrosis at the treatment site. There was 1 rib fracture. Other late toxicities included 7.4% grade 1 hyperpigmentation, 2% grade 1 telangiectasias, 1.7% symptomatic seromas, 1.7% abscessed cavities, and 1.1% symptomatic fat necrosis. There were 2 (1.1%) ipsilateral local recurrences, 2 (1.1%) nodal recurrences and no distant recurrences. Other incidents included one contralateral breast cancer and 2 second malignancies (lung). CONCLUSIONS: Ultra-short breast brachytherapy is feasible and has excellent toxicity and could be an alternative to standard 5-day, 10 fraction accelerated partial breast irradiation in eligible patients. Patients from this prospective trial will continue to be followed to evaluate long-term outcomes.
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Braquiterapia , Neoplasias de la Mama , Femenino , Humanos , Persona de Mediana Edad , Braquiterapia/efectos adversos , Braquiterapia/métodos , Neoplasias de la Mama/patología , Estudios de Seguimiento , Hospitales , Mastectomía Segmentaria , Estudios Prospectivos , Recurrencia , Resultado del TratamientoRESUMEN
Purpose: The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was designed for semi-quantitative assessment of early ischemic changes on non-contrast computed tomography (NCCT) for acute ischemic stroke (AIS). We evaluated two automated ASPECTS software in comparison with reference standard. Methods: NCCT of 276 AIS patients were retrospectively reviewed (March 2018-June 2020). A three-radiologist consensus for ASPECTS was used as reference standard. Imaging data from both baseline and follow-up were evaluated for reference standard. Automated ASPECTS were calculated from baseline NCCT with 1-mm and 5-mm slice thickness, respectively. Agreement between automated ASPECTS and reference standard was assessed using intra-class correlation coefficient (ICC). Correlation of automated ASPECTS with baseline stroke severity (NIHSS) and follow-up ASPECTS were evaluated using Spearman correlation analysis. Results: In score-based analysis, automated ASPECTS calculated from 5-mm slice thickness images agreed well with reference standard (software A: ICC = 0.77; software B: ICC = 0.65). Bland-Altman analysis revealed that the mean differences between automated ASPECTS and reference standard were ≤ 0.6. In region-based analysis, automated ASPECTS derived from 5-mm slice thickness images by software A showed higher sensitivity (0.60 vs. 0.54), lower specificity (0.91 vs. 0.94), and higher AUC (0.76 vs. 0.74) than those using 1-mm slice thickness images (p < 0.05). Automated ASPECTS derived from 5-mm slice thickness images by software B showed higher sensitivity (0.56 vs. 0.51), higher specificity (0.87 vs. 0.81), higher accuracy (0.80 vs. 0.73), and higher AUC (0.71 vs. 0.66) than those using 1-mm slice thickness images (p < 0.05). Automated ASPECTS were significantly associated with baseline NIHSS and follow-up ASPECTS. Conclusion: Automated ASPECTS showed good reliability and 5 mm was the optimal slice thickness.
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Spinal cord injury (SCI) is a devastating neurological disorder characterized by high morbidity and disability. However, there is still a lack of effective treatments for it. The identification of drugs that promote autophagy and inhibit apoptosis in neurons is critical for improving patient outcomes following SCI. Previous studies have shown that increasing the activity of silent information regulator 1 (SIRT1) and downstream protein AMP-activated protein kinase (AMPK) in rat models of SCI is highly neuroprotective. Oxymatrine (OMT), a quinolizidine alkaloid, has exhibited neuroprotective effects in various central nervous system (CNS) diseases. However, its explicit effect and molecular mechanism in SCI are still unclear. Herein, we aimed to investigate the therapeutic effects of OMT and explore the potential role of autophagy regulation following SCI in rats. A modified compressive device (weight 35 g, time 5 min) was applied to induce moderate SCI in all groups except the sham group. After treatment with drugs or vehicle (saline), our results indicated that OMT treatment significantly reduced the lesion size, promoted survival of motor neurons, and subsequently attenuated motor dysfunction following SCI in rats. OMT significantly enhanced autophagy activity, inhibited apoptosis in neurons, and increased SIRT1 and p-AMPK expression levels. Interestingly, these effects of OMT on SCI were partially prevented by co-treatment with SIRT1 inhibitor EX527. Furthermore, combining OMT with the potent autophagy inhibitor chloroquine (CQ) could effectively abolish its promotion of autophagic flux. Taken together, these data revealed that OMT exerts a neuroprotective role in functional recovery against SCI in rats, and these effects are potentially associated with OMT-induced activation of autophagy via the SIRT1/AMPK signaling pathway.
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Fármacos Neuroprotectores , Traumatismos de la Médula Espinal , Ratas , Animales , Ratas Sprague-Dawley , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Sirtuina 1/metabolismo , Traumatismos de la Médula Espinal/patología , Autofagia , Neuronas Motoras/metabolismo , Apoptosis , Médula Espinal/patología , Recuperación de la FunciónRESUMEN
BACKGROUND: Uterine clear cell and serous carcinomas have a high propensity for locoregional and distant spread, tend to be more advanced at presentation, and carry a higher risk of recurrence and death than endometrioid cancers. Limited prospective data exist to guide evidence-based management of these rare malignancies. OBJECTIVE: The American Radium Society sought to summarize evidence-based guidelines developed by a multidisciplinary expert panel that help to guide the management of uterine clear cell and serous carcinomas. METHODS: The American Radium Society Appropriate Use Criteria presented in this manuscript were developed by a multidisciplinary expert panel using an extensive analysis of current published literature from peer-reviewed journals. A well-established methodology (modified Delphi) was used to rate the appropriate use of diagnostic and therapeutic procedures for the management of uterine clear cell and serous carcinomas. RESULTS: The primary treatment for non-metastatic uterine clear cell and serous carcinomas is complete surgical staging, with total hysterectomy, salpingo-oophorectomy, omentectomy, and lymph node staging. Even in early-stage disease, patients with uterine clear cell and serous carcinomas have a worse prognosis than those with type I endometrial cancers, warranting consideration for adjuvant therapy regardless of the stage. Given the aggressive nature of these malignancies, and until further research determines the most appropriate adjuvant therapy, it may be reasonable to counsel patients about combined-modality treatment with systemic chemotherapy and radiotherapy. CONCLUSION: Patients diagnosed with uterine clear cell and serous carcinomas should undergo complete surgical staging. Multimodal adjuvant therapies should be considered in the treatment of both early-stage and advanced-stage disease. Further prospective studies or multi-institutional retrospective studies are warranted to determine optimal sequencing of therapy and appropriate management of patients based on their unique risk factors. Long-term surveillance is indicated due to the high risk of locoregional and distant recurrence.
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Cistadenocarcinoma Seroso , Neoplasias Endometriales , Radio (Elemento) , Neoplasias Uterinas , Femenino , Humanos , Radio (Elemento)/uso terapéutico , Neoplasias Uterinas/patología , Estudios Prospectivos , Radioterapia Adyuvante , Quimioterapia Adyuvante , Estadificación de Neoplasias , Neoplasias Endometriales/patología , Cistadenocarcinoma Seroso/patología , Histerectomía , Estudios RetrospectivosRESUMEN
Exhibition is a new economic business form in China. From a stakeholder perspective, all important roles in the context of hospitality and tourism are talents. From a socio-cultural perspective, interpersonal relationship quality plays a vital role in business and industrial operations. This constructs a causal model of relationship quality between exhibitors and exhibition organizers, and examined its influence on exhibitors' willingness to sustainably participate in exhibitions. Data collected from a total of 251 exhibitors from 4 nation-representative exhibitions in Beijing were analyzed. The results found that the four antecedent variables-guanxi (as distinctive from relationship quality), service quality, communication, and exhibition effectiveness-have significant impacts on the relationship quality between exhibitors and exhibition organizers, which in turn, affect exhibitors' willingness to participate in subsequent exhibitions (i.e., exhibitor loyalty). These findings provide a theoretical basis and policy recommendations talent management in exhibition context.
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BACKGROUND: Behavioral weight loss interventions are frequently hampered by long-term inefficacy. As metabolic improvements and health-related quality of life (HRQoL) are diminished by weight regain, effective long-term strategies are highly desirable. We aimed to analyze whether an additional weight maintenance intervention could delay body weight regain and can induce a long-term improvement of metabolism and HRQoL for up to 48 months in humans. Given the short-term metabolic effects of natriuretic peptides (NP), we also investigated the role of the adipose atrial NP (ANP) system in this long-term context. METHODS: After a successful 12-week weight reduction program 143 subjects (age>18; BMI≥27 kg/m2) were randomized (1:1) to a control group or a 12-month multimodal weight maintenance intervention focusing on nutritional counseling and physical exercises. Secondary trial outcomes including course of BMI, HOMA-IR, glucose response after oGTT (glucoseAUC), and HRQoL (SF-36) were analyzed yearly for 48 months. Adipose ANP receptor mRNA expression was analyzed during weight loss. RESULTS: Initial weight loss (- 4.7±1.5 kg/m2) improved glucoseAUC, HOMA-IR, and HRQoL. Although BMI was still reduced after 48 months (-1.98 [95% CI -2.61, -1.35] kg/m2), benefits on HOMA-IR, glucoseAUC, and mental health disappeared after 36 (-0.49 [-1.00, 0.02]), 18 (0.61 [-9.57, 10.79] mg dl-1 min-1), and 18 months (2.06 [-0.08, 4.20]), respectively, while improved physical health persisted up to months 48 (2.95 [0.49, 5.40]). Weight maintenance intervention inhibited weight regain and delayed impairment of HOMA-IR and glucoseAUC (but not HRQoL) for up to 12 months. However, no metabolic long-term effect was seen beyond the intervention period. Lower adipose NPR-C and higher NPR-A mRNA expression after weight loss predicted smaller regain of weight (r=0.398; p<0.05)/fat mass (FM) (r=0.391; p<0.05) and longer improvement of HOMA-IR (r=-0.422; p<0.05), respectively. CONCLUSIONS: Additional benefits of a behavioral 12-month weight maintenance intervention after weight loss regarding body weight regain and metabolic improvement does not persist beyond the intervention period. However, weight loss-induced modulation of the adipose ANP system is probably involved in the long-term control of body weight regain and insulin sensitivity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00850629 . Registered on February 25, 2009.
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Resistencia a la Insulina , Pérdida de Peso , Factor Natriurético Atrial , Índice de Masa Corporal , Mantenimiento del Peso Corporal , Glucosa , Humanos , Resistencia a la Insulina/fisiología , Obesidad/metabolismo , Calidad de Vida , ARN Mensajero , Aumento de Peso , Pérdida de Peso/fisiologíaRESUMEN
BACKGROUND: Breastfeeding education plays a crucial role in improving breastfeeding outcomes and has been employed in many medical institutions across China. OBJECTIVES: To describe the current situation of breastfeeding education provided by hospitals to women in China, and to identify relevant factors associated with the exclusive breastfeeding rate at hospital discharge and the early breastfeeding initiation rate. DESIGN: A cross-sectional study design. SETTINGS AND PARTICIPANTS: We used an online survey platform called WenjuanXing to collect data from 2985 hospitals in China. METHODS: We designed a questionnaire to collect data. The Mann-Whitney U test and Pearson's chi-square test were used to identify the differences between the different types and levels of hospitals. Binary logistic regression analysis was used to analyze the factors associated with the exclusive breastfeeding rate at hospital discharge and the early breastfeeding initiation rate. RESULTS: A total of 2941 hospitals were included in the data analysis. In 86% of hospitals midwives were providing breastfeeding education on weekdays during the daytime. Information on how to deal with mastitis (80.8%) and weaning methods (71.5%) was less commonly provided to women. The hospitals often conducted breastfeeding education through antenatal education sessions and bedside health education, while 34.2% of hospitals used smartphone applications. The obstacles to conducting breastfeeding education in hospitals were a lack of full-time staff dedicated to breastfeeding education (43.3%) and limited funds invested in breastfeeding education (42.5%). A lack of full-time staff dedicated to breastfeeding education (OR, 0.689; 95% CI, 0.498-0.953) and a lack of space (OR, 0.697; 95% CI, 0.487-0.997) were associated with the exclusive breastfeeding rate at hospital discharge. Furthermore, a lack of full-time staff dedicated to breastfeeding education (OR, 0.372; 95% CI, 0.235-0.589) was associated with the early breastfeeding initiation rate. CONCLUSIONS: To improve breastfeeding outcomes, hospital managers and policymakers should increase the number of midwives and full-time staff who are dedicated to breastfeeding education, resolve the obstacles of limited funds and space for breastfeeding education, and explore more approaches to providing knowledge on breastfeeding to women and their families.
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Lactancia Materna , Hospitales , China , Estudios Transversales , Femenino , Humanos , Madres/educación , Embarazo , Encuestas y CuestionariosRESUMEN
Evidence suggests that macrophage pyroptosis promotes the progression of diabetic atherosclerosis. Spermine, a natural cellular metabolite, demonstrates a protective effect against cardiovascular diseases. However, whether spermine has a protective effect against macrophage pyroptosis caused by high glucose (HG) and oxidized low-density lipoprotein (ox-LDL) conditions remains to be elucidated. To investigate the protective effect of spermine and the related underlying mechanism, THP-1 macrophages were treated with HG/ox-LDL, spermine, or the specific nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385. Cell viability was detected using CCK-8, cell membrane permeability was analyzed using lactate dehydrogenase (LDH) and Hoechst/propidium iodide staining and pyroptosis-related gene and protein expression levels were evaluated using polymerase chain reaction and western blot analysis. Spermine showed a potent preventive effect on THP-1 macrophage pyroptosis and oxidative stress induced by HG/ox-LDL. Cells treated with spermine showed increased cell viability, reduced reactive oxygen species (ROS) production, decreased LDH levels in the supernatant and reduced cell swelling. In addition, spermine significantly reduced NLR family pyrin domain containing 3, cleaved caspase-1, N-gasdermin D and IL-1ß expression, as well as IL-1ß levels in the supernatant. This demonstrated that the inhibition of pyroptosis and oxidative stress due to spermine was Nrf2 dependent. Furthermore, spermine enhanced Nrf2 nuclear translocation, thereby increasing heme oxygenase-1 and NADPH quinone oxidoreductase-1 expression, which subsequently reduced ROS production. In addition, the anti-pyroptotic and antioxidant effects of spermine were reversed by ML385 inhibition of Nrf2. It was concluded that spermine prevented macrophage pyroptosis and increased ROS overproduction by activating the Nrf2 pathway. The data suggested that spermine may be a potential novel drug for the treatment of diabetic atherosclerosis because it targets macrophage pyroptosis.
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BACKGROUND & AIMS: Sustained weight loss is highly desirable in obesity. Although the role of incretins in the regulation of body weight is well known, macronutrient specific incretin response and the effects of weight loss on this response have not been investigated before. We aimed to examine GLP-1, GIP, ghrelin, insulin, and satiety response to meals with different macronutrient composition in overweight and obese subjects before and after weight loss. METHODS: 32 overweight and obese participants underwent meal tests before and after weight loss intervention. Test meals were designed to be either carbohydrate (CHO), fat (FAT), or protein (PRO) enriched to test macronutrient specific response. Macronutrient specific response of GLP-1, GIP, and ghrelin before and after weight loss were the primary outcome measures. Response of insulin and satiety were predefined secondary endpoints. RESULTS: There were macronutrient specific response patterns of GLP-1 (PRO>FAT=CHO), GIP (CHO=FAT>PRO), and insulin (CHO>PRO=FAT). Postprandial decline of ghrelin did not differ between the test meals. Hunger, desire to eat, and prospective food consumption were highest after CHO intake (CHO>PRO=FAT) at baseline. After weight loss, fasting and postprandial GLP-1 and insulin were reduced while concomitant ghrelin levels were increased. However, the macronutrient specific hormonal response pattern did not change after weight loss. While weight loss increased hunger and desire to eat, the macronutrient specific differences were lost after weight reduction. Higher weight loss was associated with a stronger decline of PRO induced GLP-1 response (ρ = 0.45, p = 0.024, n = 27). CONCLUSIONS: Both hormones and satiety showed a macronutrient specific response in overweight/obese participants with a possibly favorable role of protein. However, weight loss may cause a partial disruption of this hormone-satiety-connection as macronutrient specific response pattern of satiety scores representing impulse control in particular but not incretins disappeared. TRIAL REGISTRATION: NCT02649907. https://clinicaltrials.gov/ct2/show/NCT02649907.
Asunto(s)
Enfermedades Metabólicas , Sobrepeso , Estudios Cruzados , Ghrelina , Humanos , Insulina , Nutrientes , Obesidad/metabolismo , Obesidad/terapia , Sobrepeso/terapia , Periodo Posprandial , Pérdida de PesoRESUMEN
Cone-shaped corneas are blinding eye diseases characterised by dilated and thinning corneal tissue and forward conical protrusions, most often in adolescents. Early detection and intervention can prevent further dilatation of the cornea. The prevailing examination methods and techniques are not difficult to diagnose clinical cone corneas, but there are limitations in the diagnosis of early cone corneas (static cone corneas and subclinical cone corneas). In this study, we investigated the diagnostic value of the combination of these two instruments in the diagnosis of clinical cone corneas and subclinical cone corneas by performing the Pentacam and Corvis ST examinations in healthy eyes and dystrophic cone corneas. This study provides a theoretical basis for early cone cornea screening and diagnosis. The analysis revealed that only TP, SPA1, ARTh, and bIOP were normally distributed among all included parameters, and only bIOP was normally distributed with equal variance. TBI and CBI indices have a certain sensitivity and specificity for the diagnosis of subclinical cone corneas, with a strong diagnostic ability, and can be used for screening and early diagnosis of cone corneas.