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1.
BMC Anesthesiol ; 24(1): 197, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834948

RESUMEN

BACKGROUND: Ciprofol is a promising sedative. This study aims to explore the median effective dose (ED50) of ciprofol in inhibiting responses to fiberoptic bronchoscopy in patients with pulmonary tuberculosis (PTB) of different genders and ages when combined with 0.15 µg/kg sufentanil, and to evaluate its efficacy and safety, providing a reference for the rational use of ciprofol in clinical practice. METHODS: PTB patients who underwent bronchoscopy examination and treatment at The Third People's Hospital of Changzhou between May 2023 and June 2023 were selected and divided into four groups using a stratified random method. All patients received intravenous injection of 0.15 µg/kg sufentanil followed by injection of the test dose of ciprofol according to Dixon's up-and-down method. The initial dose of ciprofol in all four groups was 0.4 mg/kg, with an adjacent ratio of 1:1.1. The next patient received a 10% increase in the dose of ciprofol if the previous patient in the same group experienced positive reactions such as choking cough, frowning, and body movements during the endoscopy. Otherwise, it was judged as a negative reaction, and the next patient received a 10% decrease in the dose of ciprofol. The transition from a positive reaction to a negative reaction was defined as a turning point, and the study of the group was terminated when seven turning points occurred. Hemodynamic parameters, oxygen saturation and adverse reactions were recorded at different time points in all groups. The Probit regression analysis method was used to calculate the ED50 of ciprofol in the four groups and compare between the groups. RESULTS: The ED50 of ciprofol combined with 0.15 µg/kg sufentanil for bronchoscopy in the four groups were 0.465 mg/kg, 0.433 mg/kg, 0.420 mg/kg and 0.396 mg/kg, respectively. CONCLUSION: The ED50 of ciprofol used for fiberoptic bronchoscopy varied among PTB patients of different genders and ages. TRIAL REGISTRATION: The Chinese Clinical Trial Registry, ChiCTR2300071508, Registered on 17 May 2023.


Asunto(s)
Broncoscopía , Tecnología de Fibra Óptica , Sufentanilo , Tuberculosis Pulmonar , Humanos , Masculino , Broncoscopía/métodos , Femenino , Persona de Mediana Edad , Sufentanilo/administración & dosificación , Adulto , Tuberculosis Pulmonar/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Anciano , Hipnóticos y Sedantes/administración & dosificación , Adulto Joven , Quimioterapia Combinada
2.
J Biol Chem ; 298(4): 101768, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35218776

RESUMEN

As a crucial metabolic intermediate, l-lactate is involved in redox balance, energy balance, and acid-base balance in organisms. Moderate exercise training transiently elevates plasma l-lactate levels and ameliorates obesity-associated type 2 diabetes. However, whether moderate l-lactate administration improves obesity-associated insulin resistance remains unclear. In this study, we defined 800 mg/kg/day as the dose of moderate l-lactate administration. In mice fed with a high-fat diet (HFD), moderate l-lactate administration for 12 weeks was shown to alleviate weight gain, fat accumulation, and insulin resistance. Along with the phenotype alterations, white adipose tissue thermogenesis was also found to be elevated in HFD-fed mice. Meanwhile, moderate l-lactate administration suppressed the infiltration and proinflammatory M1 polarization of adipose tissue macrophages (ATMs) in HFD-fed mice. Furthermore, l-lactate treatment suppressed the lipopolysaccharide-induced M1 polarization of bone marrow-derived macrophages (BMDMs). l-lactate can bind to the surface receptor GPR132, which typically drives the downstream cAMP-PKA signaling. As a nutrient sensor, AMP-activated protein kinase (AMPK) critically controls macrophage inflammatory signaling and phenotype. Thus, utilizing inhibitors of the kinases PKA and AMPK as well as siRNA against GPR132, we demonstrated that GPR132-PKA-AMPKα1 signaling mediated the suppression caused by l-lactate treatment on BMDM M1 polarization. Finally, l-lactate addition remarkably resisted the impairment of lipopolysaccharide-treated BMDM conditional media on adipocyte insulin sensitivity. In summary, moderate l-lactate administration suppresses ATM proinflammatory M1 polarization through activation of the GPR132-PKA-AMPKα1 signaling pathway to improve insulin resistance in HFD-fed mice, suggesting a new therapeutic and interventional approach to obesity-associated type 2 diabetes.


Asunto(s)
Tejido Adiposo , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Ácido Láctico , Macrófagos , Obesidad , Proteínas Quinasas Activadas por AMP/metabolismo , Tejido Adiposo/citología , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Dieta Alta en Grasa , Inflamación/metabolismo , Resistencia a la Insulina/genética , Ácido Láctico/administración & dosificación , Ácido Láctico/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/genética , Transducción de Señal/efectos de los fármacos , Aumento de Peso/efectos de los fármacos
3.
J Am Chem Soc ; 145(41): 22671-22684, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37814206

RESUMEN

Multicomponent alloy (MA) contains a nearly infinite number of unprecedented active sites through entropy stabilization, which is a desired platform for exploring high-performance catalysts. However, MA catalysts are usually synthesized under severe conditions, which induce support structure collapse and further deteriorate the synergy between MA and support. We propose that a strong metal-support interaction (SMSI) could facilitate the formation of MA by establishing a tunnel of oxygen vacancy for metal atom transport under low reduction temperature (400-600 °C), which exemplifies the holistic design of MA catalysts without deactivating supports. PtPdCoFe MA is readily synthesized on anatase TiO2 with the help of SMSI, which exhibits good catalytic activity and stability for methane combustion. This strategy demonstrates excellent universality on various supports and multicomponent alloy compositions. Our work not only reports a holistic synthesis strategy for MA synthesis by synergizing unique properties of reducible oxides and the mixing entropy of alloy but also offers a new insight that SMSI plays a vigorous role in the formation of alloy NPs on reducible oxides.

4.
Liver Transpl ; 29(6): 607-617, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36748552

RESUMEN

Biliary atresia (BA) is the most common indication for pediatric liver transplantation, and biliary stricture (BS) remains an Achilles' heel for pediatric living donor liver transplantation (LDLT). We investigated the impact of different ischemia times on BS after LDLT in patients with BA. We retrospectively analyzed patients (<18 y) with BA who underwent LDLT between January 2016 and December 2020. Cases with hepatic artery thrombosis, bile leakage, early BS (<2 wk), and early death (<3 mo) were excluded. In all, 572 cases were included. A total of 26 cases (4.55%, 26/572) developed BS: 25 patients with anastomotic stricture and 1 patient with anastomotic stricture combined with left hepatic duct stricture. In addition, the time to diagnosis of BS ranged from 1.8 to 53.0 months (mean, 13.0 mo and median, 8.2 mo) after transplantation. A multivariate logistic regression analysis showed that arterial ischemia time (AIT), per 10 minutes (OR=1.222, 95% CI: 1.007-1.438, p =0.04) was the only independent risk factor for the development of BS after LDLT in patients with BA. What is more, the 5-year cumulative risk of BS between the AIT ≥40 minutes and AIT <40 minutes groups was 2.79% versus 10.57%. AIT was the only independent risk factor for the development of BS after LDLT with BA, and AIT ≥40 minutes would increase the 5-year cumulative risk of BS in our study. A shorter AIT, especially AIT <40 minutes, should be kept to decrease BS.


Asunto(s)
Atresia Biliar , Colestasis , Trasplante de Hígado , Humanos , Niño , Trasplante de Hígado/efectos adversos , Atresia Biliar/cirugía , Atresia Biliar/complicaciones , Donadores Vivos , Constricción Patológica/etiología , Estudios Retrospectivos , Anastomosis Quirúrgica/efectos adversos , Colestasis/etiología , Isquemia/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología
5.
Endoscopy ; 55(4): 324-331, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-35998673

RESUMEN

BACKGROUND: Water exchange colonoscopy is the least painful method for unsedated colonoscopies. Simplified left colon water exchange (LWE) reduces the cecal intubation time but it is difficult to avoid the use of an additional pump. Minimal water exchange (MWE) is an improved novel method that eliminates the need for pumps, but it is not clear whether MWE has the same efficiency as LWE. METHODS: This was a prospective, randomized, controlled, noninferiority trial conducted in a tertiary hospital. Enrolled patients were randomized 1:1 to the LWE group or MWE group. The primary outcome was recalled insertion pain measured by a 4-point verbal rating scale. Secondary outcomes included adenoma detection rate (ADR), cecal intubation time, volume of water used, and patient willingness to repeat unsedated colonoscopy. RESULTS: 226 patients were included (LWE n = 113, MWE n = 113). The MWE method showed noninferior moderate/severe pain rates compared with the LWE method (10.6 % vs. 9.7 %), with a difference of 0.9 percentage points (99 % confidence interval [CI] -9.5 to 11.3; threshold, 15 %). ADR, cecal intubation time, and willingness to repeat unsedated colonoscopy were not significantly different between the two groups, but the mean volume of water used was significantly less with MWE than with LWE (163.7 mL vs. 407.2 mL; 99 %CI -298.28 to -188.69). CONCLUSION: Compared with LWE, MWE demonstrated a noninferior outcome for insertion pain, and comparable cecal intubation time and ADR, but reduced the volume of water used and eliminated the need for a water pump.


Asunto(s)
Adenoma , Insuflación , Humanos , Colonoscopía/métodos , Ciego , Agua , Estudios Prospectivos , Insuflación/métodos , Colon , Dolor , Adenoma/diagnóstico
6.
Clin Transplant ; 37(2): e14894, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36581321

RESUMEN

INTRODUCTION: Subclinical rejection (SCR) is a common injury in protocol biopsy after pediatric liver transplantation (pLT), but its effect on the recipient is not clearly understood. We herein investigated the incidence and risk factors involved in SCR and analyzed the relationship between SCR and allograft fibrosis (AF). METHODS: We retrospectively reviewed the biopsy results from 507 children between May 2013 and May 2019, and 352 patients underwent protocol biopsy 2 years after pLT, 203 underwent protocol biopsy 5 years after pLT, and 48 underwent protocol biopsy both 2 and 5 years after pLT. RESULTS: The incidence of SCR in the 5-year group was higher than that in the 2-year group (20.2% vs.13.4%, respectively, p = .033). The number of patients with mild and moderate SCR in the 5-year group was also higher than that in the 2-year group (p = .039). Logistic regression analysis showed that acute rejection before liver biopsy and deceased donor liver transplantation (DDLT) were independent risk factors for SCR in the two groups, and that the incidence and severity of AF in protocol biopsies at both periods in the SCR group were higher than those in the non-SCR group (p < .05). CONCLUSIONS: The incidence and severity of SCR increased with the prolongation of protocol biopsy time. We postulate that acute rejection and DDLT are independent risk factors for SCR after transplantation. As the occurrence of SCR also augmented the incidence and severity of AF.


Asunto(s)
Trasplante de Riñón , Trasplante de Hígado , Humanos , Niño , Trasplante de Hígado/efectos adversos , Trasplante de Riñón/efectos adversos , Incidencia , Estudios Retrospectivos , Rechazo de Injerto/epidemiología , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Donadores Vivos , Factores de Riesgo , Fibrosis , Biopsia , Aloinjertos/patología
7.
Scand J Gastroenterol ; 58(3): 248-253, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36111683

RESUMEN

BACKGROUND: Circular RNA (circRNA) is a kind of endogenous non-coding RNAs and has shown diagnostic values in various cancers. This study aimed to explore whether hsa_circ_0001789 could be a novel biomarker for gastric cancer (GC). METHODS: Quantitative reverse transcriptase PCR was used to detect the expression of hsa_circ_0001789 in 108 paired GC and paracancerous tissues as well as in 24 paired plasma specimens. Possible associations between hsa_circ_0001789 expression and clinicopathologic factors of GC patients were examined using one-way ANOVA. A receiver operating characteristic (ROC) curve was established to investigate the diagnostic value of hsa_circ_0001789 in GC. RESULTS: GC tissues and plasma samples showed down-regulated hsa_circ_0001789 levels than their counterparts, which were closely correlated with the malignant characteristics of GC. The area under the ROC curve (AUC) of hsa_circ_0001789 in GC tissues was 0.82, while the cut-off value was 9.5, indicating a favorable diagnostic value. Compared with the traditional tumor biomarkers, hsa_circ_0001789 had preferred AUCs that reached 0.786 for predicting the stage of invasion, 0.603 for predicting the stage of lymphatic metastasis, 0.722 for predicting the stage of distant metastasis, and 0.786 for predicting TNM stage. CONCLUSIONS: Hsa_circ_0001789 may be a novel biomarker for the diagnosis of gastric carcinoma.


Asunto(s)
Carcinoma , Neoplasias Gástricas , Humanos , ARN Circular/genética , ARN/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Biomarcadores de Tumor/metabolismo , Curva ROC , Regulación Neoplásica de la Expresión Génica
8.
Eur J Nutr ; 62(1): 379-383, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36040623

RESUMEN

BACKGROUND AND AIM: Prospective cohort studies have suggested that sugar-sweetened beverages (SSBs) intake is significantly associated with the risk of colorectal cancer (CRC). However, it remains unclear whether this observed association was susceptible to potential confounding factors due to the long-term development process of CRC, and the risk of CRC associated with sweet beverages has rarely been reported. We aimed to investigate the association between SSBs/sweet beverages and CRC risk. METHODS: We performed two-sample Mendelian randomization (MR) analysis using independent genetic variants for SSBs and sweet beverages from a published genome-wide association study (GWAS). Summary statistics for instrument-outcome associations from two databases for malignant neoplasms of the colon and the rectum (FinnGen and UK Biobank). The inverse weighted method (IVW) meta-analysis was the main method used to estimate the relationship, and sensitivity analyses were performed with Cochran's Q test, leave-one-out analysis, MR-Egger regression, Steiger filtering, and the MR PRESSO test. RESULTS: Genetically predicted SSBs intake was associated with a higher colonic malignant neoplasms risk (odds ratio (OR): 1.013; 95% confidence interval (CI) 1.001, 1.026; P = 0.036) in a combined sample size of 579,986 individuals (4029 cases). Such a significant causal effect of SSBs on rectal malignant neoplasms or sweet beverages on CRC was not observed. CONCLUSION: Our findings corroborated a causal association between SSBs and colonic malignant neoplasms risk but did not support such a relationship in the analysis of the rectal malignant neoplasms nor the sweet beverage intake, which might be interpreted with caution and further confirmed.


Asunto(s)
Neoplasias Colorrectales , Bebidas Azucaradas , Humanos , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Bebidas Azucaradas/efectos adversos
9.
Pediatr Transplant ; 27(5): e14501, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36906739

RESUMEN

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious complication after pediatric liver transplantation (pLT), which may lead to death. 18 F-FDG PET/CT is rarely considered in PTLD after pLT and lacks clear diagnostic guidelines, especially in the differential diagnosis of nondestructive PTLD. The aim of this study was to find a quantifiable 18 F-FDG PET/CT index to identify nondestructive PTLD after pLT. METHODS: This retrospective study collected the data of patients who underwent pLT, postoperative lymph node biopsy, and 18 F-FDG PET/CT at Tianjin First Central Hospital from January 2014 to December 2021. Quantitative indexes were established using lymph node morphology and the maximum standardized uptake value (SUVmax). RESULTS: A total of 83 patients met the inclusion criteria and were included in this retrospective study. To distinguish between PTLD-negative cases and nondestructive PTLD cases, according to the receiver operating characteristic curve, (the shortest diameter of the lymph node at the biopsy site [SDL]/the longest diameter of the lymph node at the biopsy site [LDL])*(SUVmax at the biopsy site [SUVmaxBio]/SUVmax of the tonsils [SUVmaxTon]) had the maximum area under the curve (0.923; 95% confidence interval: 0.834-1.000), and the cutoff value was 0.264 according to the maximum value of Youden's index. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 93.6%, 94.7%, 97.8%, 85.7%, and 93.9%, respectively. CONCLUSIONS: (SDL/LDL)*(SUVmaxBio/SUVmaxTon) has good sensitivity, specificity, positive predictive and negative predictive values, and accuracy, and can be used as a good quantitative index for the diagnosis of nondestructive PTLD.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Trasplante de Hígado , Trastornos Linfoproliferativos , Humanos , Niño , Tomografía Computarizada por Tomografía de Emisión de Positrones/efectos adversos , Fluorodesoxiglucosa F18 , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Tomografía de Emisión de Positrones/efectos adversos , Trastornos Linfoproliferativos/diagnóstico por imagen , Trastornos Linfoproliferativos/etiología , Infecciones por Virus de Epstein-Barr/complicaciones , Radiofármacos
10.
BMC Public Health ; 23(1): 714, 2023 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-37076853

RESUMEN

OBJECTIVES: Myocarditis, a health-threatening heart disease, is attracting increasing attention. This systematic study was conducted to study the prevalence of disease through the trends of incidence, mortality, disability-adjusted life years (DALYs) over the last 30 years, which would be helpful for the policymakers to better the choices for reasonable decisions. METHODS: The global, regional, and national burdens of myocarditis from 1990-2019 were analyzed by using the 2019 Global Burden of Disease (GBD) database. This study on myocarditis produced new findings according to age, sex, and Social-Demographic Index (SDI) by investigating DALYs, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and corresponding estimated annual percentage change (EAPC). RESULTS: The number of myocarditis incidence increased by 62.19%, from 780,410 cases in 1990 to 1,265,770 cases in 2019. The ASIR decreased by 4.42% (95%CI, from -0.26% to -0.21%) over the past 30 years. The number of deaths from myocarditis increased by 65.40% from 19,618 in 1990 to 324,490 in 2019, but the ASDR was relatively stable over the investigated period. ASDR increased in low-middle SDI regions (EAPC=0.48; 95%CI, 0.24 to 0.72) and decreased in low SDI regions (EAPC=-0.97; 95%CI, from -1.05 to -0.89). The age-standardized DALY rate decreased by 1.19% (95%CI, from -1.33% to -1.04%) per year. CONCLUSIONS: Globally, the ASIR and DALY for myocarditis decreased and the ASDR was stable over the past 30 years. The risk of incidences and death cases increased with age. Measures should be taken to control the risk of myocarditis in high-burden regions. Medical supplies should be improved in the high-middle SDI regions and middle SDI regions to reduce the deaths from myocarditis in these regions.


Asunto(s)
Carga Global de Enfermedades , Miocarditis , Humanos , Años de Vida Ajustados por Calidad de Vida , Miocarditis/epidemiología , Salud Global , Años de Vida Ajustados por Discapacidad , Incidencia
11.
Altern Ther Health Med ; 29(1): 176-181, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36074967

RESUMEN

Context: Of the 26-million people suffering from heart failure worldwide, 80% require hospitalization for treatment every year. Biomarkers for clinical diagnosis and prognostic evaluation of heart failure may include: (1) growth-stimulating expression gene 2 protein (sST2), (2) blood urea nitrogen (BUN) and creatinine (Cr), (3) cardiac troponin I (CTnI), and (4) brain-derived neurotrophic factor (BDNP). At present, few studies have occurred on the expression of those biomarkers in patients with heart failure. Objective: The study intended to investigate the expression and clinical significance of serum- soluble sST2, BDNF, CTnI, and BUN/Cr in patients with heart failure. Design: The research team designed a prospective controlled study. Setting: The study took place at Renmin Hospital at the Hubei University of Medicine in Shiyan, Hubei, China. Participants: Participants were 108 patients with heart failure who had been admitted to the hospital between March 2020 and March 2021 and 115 healthy individuals who received physical examinations during the same period. Intervention: The intervention group included the 108 participants with heart failure, and the control group included the healthy individuals. The research team further divided the intervention group into stage II, III, and IV groups, with 23, 65, and 20 patients, respectively. Outcome Measures: The research team collected and compared the serum levels of sST2, BDNF, CTnI, BUN/Cr, and left ventricular ejection fraction (LVEF) between the groups. The team used the Pearson correlation analysis to analyze the correlation between each parameter and participants' cardiac function and multivariate logistic regression analysis to analyze the factors influencing heart failure. Results: No significant differences existed in age, gender, or disease course between the combined intervention groups and the control group at baseline (P > .05). The sST2, CTnI, and BUN/Cr levels of the combined intervention groups were significantly higher than those of the control group postintervention. In addition, the sST2, CTnI, and BUN/Cr levels significantly increased as the disease stage progressed (all P < .05). The levels of BDNF and LVEF in the combined intervention group were significantly lower than those in the control group postintervention, with the two parameters having significantly decreased in the intervention groups as the disease stage progressed (all P < .05). The Pearson correlation analysis found that the sST2, CTnI, and BUN/Cr were positively correlated with cardiac function, with r = 0.483, P = .017; r = .521, P = .011; r = 0.321, P = .021; r = 0.271, = .032; and r = 0.632, P = .007, respectively. The BDNF and LVEF were negatively correlated with cardiac function, with r = -0.43, P < .001 and r = -0.39, P < .001, respectively. With heart failure as the dependent variable, the logistic regression analysis showed that the sST2, CTnI, BUN, Cr, and BUN/Cr were the risk factors for heart failure, and the BDNF and LVEF were the protective factors against heart failure. Conclusions: The serum sST2, CTnI, and BUN/Cr were highly expressed in patients with heart failure, while the expression of BDNF was low. Medical practitioners should pay attention to the risk factors sST2, CTnI, and BUN/Cr, and a higher BNDF indicates a better condition in patients with heart failure.


Asunto(s)
Insuficiencia Cardíaca , Función Ventricular Izquierda , Humanos , Volumen Sistólico , Troponina I , Nitrógeno de la Urea Sanguínea , Estudios Prospectivos , Relevancia Clínica , Factor Neurotrófico Derivado del Encéfalo , Insuficiencia Cardíaca/diagnóstico , Biomarcadores
12.
Drug Dev Res ; 84(2): 312-325, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36658741

RESUMEN

Copper ions play a crucial role in the progression of cancers. Tumor tissue is rich in copper ions, and copper chelators could potentially scavenge these copper ions and thus exert an antitumor effect. In this study, we report the synthesis of a novel thieno[3,2-c]pyridine compound we have called "JYFY-001" that can act as the copper chelator thanks to the inclusion of an N-(pyridin-2-yl)acetamide moiety that targets copper ions. JYFY-001 potently inhibited cancer proliferation, inducing cell apoptosis and impairing the extracellular acidification rate and oxygen consumption rate of colorectal cancer (CRC) cells. JYFY-001 also inhibited the growth of a CRC-transplanted tumor in a dose-dependent manner, inducing apoptosis of the tumor cells and promoting the infiltration of lymphocytes in the CRC-transplanted tumor tissues. JYFY-001 also enhanced the antitumor effects of the programmed cell death protein 1 (PD-1) inhibitor. The relatively benign nature of JYFY-001 was demonstrated by the effect on normal cell viability and acute toxicity tests in mice. Our findings suggest that JYFY-001 is a prospective copper chelator to be used as a targeted drug and a synergist of immunotherapy for CRC treatments.


Asunto(s)
Neoplasias Colorrectales , Cobre , Ratones , Animales , Cobre/farmacología , Cobre/uso terapéutico , Estudios Prospectivos , Apoptosis , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Quelantes/farmacología , Quelantes/uso terapéutico , Iones/farmacología , Iones/uso terapéutico , Proliferación Celular , Línea Celular Tumoral
13.
J Environ Manage ; 330: 117108, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36584472

RESUMEN

Seagrass systems are in decline, mainly due to anthropogenic pressures and ongoing climate change. Implementing seagrass protection and restoration measures requires accurate assessment of suitable habitats. Commonly, such assessments have been performed using single-algorithm habitat suitability models, nearly always based on low environmental resolution information and short-term species data series. Here we address eelgrass (Zoostera marina) meadows' large-scale decline (>80%) in Shandong province (Yellow Sea, China) by developing an ensemble habitat model (EHM) to inform eelgrass conservation and restoration strategies in the Swan Lake (SL). For this, we applied a weighted EHM derived from ten single-algorithm models including profile, regression, classification, and machine learning methods to generate a high-resolution habitat suitability map. The EHM was constructed based on the predictive performances of each model, by combining a series of present-absent eelgrass datasets from recent years coupled with oceanographic and sediment data. The model was cross-validated with independent historical datasets, and a final habitat suitability map for conservation and restoration was generated. Our EHM scheme outperformed all single models in terms of habitat suitability, scoring ∼0.95 for both true statistic skill (TSS) and area under the curve (AUC) performance criteria. Machine learning methods outperformed profile, regression and classification methods. Regarding model explanatory variables, overall, topographic characteristics such as depth (DEP) and seafloor slope (SSL) are the most significant factors determining the distribution of eelgrass. The EHM predicted that the overlapping area was almost 90% of the current eelgrass habitat. Using results from our EHM, a LOESS regression model for the relationship of the habitat suitability to both the biomass and density of Z. marina outperformed better than the classic Ordinary Least Squares regression model. The EHM is a promising tool for supporting eelgrass protection and restoration areas in temperate lagoons as data availability improves.


Asunto(s)
Ecosistema , Zosteraceae , Biomasa , Cambio Climático , China
14.
Hum Mutat ; 43(5): 568-581, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35143101

RESUMEN

Genome sequencing (GS) has been used in the diagnosis of global developmental delay (GDD)/intellectual disability (ID). However, the performance of GS in patients with inconclusive results from chromosomal microarray analysis (CMA) and exome sequencing (ES) is unknown. We recruited 100 pediatric GDD/ID patients from multiple sites in China from February 2018 to August 2020 for GS. Patients have received at least one genomic diagnostic test before enrollment. Reanalysis of their CMA/ES data was performed. The yield of GS was calculated and explanations for missed diagnoses by CMA/ES were investigated. Clinical utility was assessed by interviewing the parents by phone. The overall diagnostic yield of GS was 21%. Seven cases could have been solved with reanalysis of ES data. Thirteen families were missed by previous CMA/ES due to improper methodology. Two remained unsolved after ES reanalysis due to complex variants missed by ES, and a CNV in untranslated regions. Follow-up of the diagnosed families revealed that nine families experienced changes in clinical management, including identification of targeted treatments, cessation of unnecessary treatment, and considerations for family planning. GS demonstrated high diagnostic yield and clinical utility in this undiagnosed GDD/ID cohort, detecting a wide range of variant types of different sizes in a single workflow.


Asunto(s)
Discapacidad Intelectual , Niño , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/genética , Humanos , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Análisis por Micromatrices/métodos , Estudios Prospectivos , Secuenciación del Exoma
15.
Cancer Sci ; 113(9): 3018-3031, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35635239

RESUMEN

Previous studies have reported that TIFA plays different roles in various tumor types. However, the function of TIFA in colorectal cancer (CRC) remains unclear. Here, we showed that the expression of TIFA was markedly increased in CRC versus normal tissue, and positively correlated with CRC TNM stages. In agreement, we found that the CRC cell lines show increased TIFA expression levels versus normal control. The knockdown of TIFA inhibited cell proliferation but had no effect on cell apoptosis in vitro or in vivo. Moreover, the ectopic expression of TIFA enhanced cell proliferation ability in vitro and in vivo. In contrast, the expression of mutant TIFA (T9A, oligomerization site mutation; D6, TRAF6 binding site deletion) abolished TIFA-mediated cell proliferation enhancement. Exploration of the underlying mechanism revealed that the protein synthesis-associated kinase RSK and PRAS40 activation were responsible for TIFA-mediated CRC progression. In summary, these findings suggest that TIFA plays a role in mediating CRC progression. This could provide a promising target for CRC therapy.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Neoplasias Colorrectales , Sitios de Unión , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Humanos , Proteínas Quinasas/metabolismo , Factor 6 Asociado a Receptor de TNF/metabolismo
16.
Crit Rev Food Sci Nutr ; : 1-15, 2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36300856

RESUMEN

Obesity is characterized by excessive body fat accumulation and is a high-risk factor for metabolic comorbidities, including type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. In lean individuals, adipose tissue (AT) is not only an important regulatory organ for energy storage and metabolism, but also an indispensable immune and endocrine organ. The sustained energy imbalance induces adipocyte hypotrophy and hyperplasia as well as AT remodeling, accompanied by chronic low-grade inflammation and adipocytes dysfunction in AT, ultimately leading to systemic insulin resistance and ectopic lipid deposition. Luteolin is a natural flavonoid widely distributed in fruits and vegetables and possesses multifold biological activities, such as antioxidant, anticancer, and anti-inflammatory activities. Diet supplementation of this flavonoid has been reported to inhibit AT lipogenesis and inflammation as well as the ectopic lipid deposition, increase AT thermogenesis and systemic energy expenditure, and finally improve obesity and associated metabolic diseases. The purpose of this review is to reveal the nutritional activities of luteolin in obesity and its complications with emphasis on its action on AT energy metabolism, immunoregulation, and endocrine intervention.

17.
Int J Colorectal Dis ; 37(6): 1223-1229, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35467123

RESUMEN

BACKGROUND: Several models for predicting adequate bowel preparation are available but have never been externally validated. The aim of this study is to compare the available models in an independent population. METHODS: This study prospectively recruited 500 consecutive patients from August to December 2020 from the Endoscopy Center of a tertiary hospital. All patients underwent the same bowel preparation regimen. The discrimination of the prediction models was quantified with the area under the receiver operating characteristic curve (AUC), and the 95% confidence interval (CI) was calculated for each AUC. RESULTS: Finally, 461 patients were eligible for this study. A total of 110 (23.9%) patients were deemed to show inadequate bowel preparation during colonoscopy. There were significant differences between patients with and without adequate bowel preparation in terms of current hospitalization, procedure time, comorbidities (including diabetes and constipation), American Society of Anesthesiologists Physical Status Classification System score (ASA) ≥ 3, medication usage, and abdominal/pelvic surgery. The prediction models performed as follows: the Dik ≥ 2 model, the Dik ≥ 3 model, and the Antonio > 1.225 model had AUCs of 0.660 (95% CI = 0.604-0.717), 0.691 (95% CI = 0.646-0.733), and 0.645 (95% CI = 0.615-0.704), respectively. Comparison of the two prediction models showed no significant improvement (Antonio > 1.225 vs. Dik ≥ 3, 1.801, 95% CI = -0.004-0.096, P = 0.072). CONCLUSIONS: Both models are potentially helpful. However, it is necessary to develop or improve a prediction model to obtain a more suitable and detailed model. TRIAL REGISTRATION: ClinicalTrials.gov, Number NCT04607161.


Asunto(s)
Catárticos , Colonoscopía , Colonoscopía/métodos , Estreñimiento/epidemiología , Humanos , Estudios Prospectivos , Curva ROC
18.
BMC Cardiovasc Disord ; 22(1): 215, 2022 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-35546659

RESUMEN

BACKGROUND: This study aimed to explore clinical value and expression of Homer 1, S-adenosyl-l-homocysteine (SAH), homocysteine (Hcy), fibroblast growth factors (FGF) 23 in coronary heart disease (CHD). METHODS: From March 2020 to April 2021, a total of 137 patients with CHD and 138 healthy subjects who came to our hospital for physical examination and had no cardiovascular disease were retrospectively enrolled, and they were assigned to the CHD group and the control group, respectively. Patients in the CHD group were divided into stable angina pectoris (SAP) group (n = 48), unstable angina pectoris (UAP) group (n = 46), and acute myocardial infarction (AMI) group (n = 43) according to clinical characteristics for subgroup analysis. The degree of coronary artery stenosis was assessed by Gensini score, which is a reliable assessment tool for the severity of coronary artery disease. The levels of Homer 1, SAH, Hcy, and FGF 23 were tested and compared. Spearman correlation analysis was used to analyze the correlation between serum Homer1, SAH, Hcy, FGF23 levels and Gensini score, and multivariate unconditional Logistic regression was used to analyze the risk factors of coronary heart disease. RESULTS: Demographic characteristics of each group were comparable (P > 0.05). The body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and glucose levels of the SAP group, UAP group and AMI group were significantly higher than those of the control group, and the number of patients with smoking, alcohol consumption, hypertension, and diabetes history was significantly more than that of the control group, respectively (P < 0.05). The level of high-density lipoprotein cholesterol (HDL-C) of each subgroup was significantly lower than the control group (P < 0.05). The above indicators showed no significant difference among three subgroups (P > 0.05). Serum SAH, Hcy, Homer1 and FGF23 levels in each subgroup were significantly higher than those in control group (P < 0.05). And above indicators in SAP group and UAP group were significantly lower than those in AMI group (P < 0.05), and the levels of above indicators in SAP group were significantly lower than those in UAP group (P < 0.05). The results of Spearman correlation analysis showed that serum Homer1, FGF23, SAH, Hcy levels were positively correlated with Gensini score (r = 0.376, 0.623, 0.291, 0.372, all P < 0.01). Multivariate logistic regression analysis showed that smoking, hypertension, diabetes, alcohol consumption, obesity, HDL-C, FGF23, SAH, Hcy, Homer 1 were independent risk factors for coronary heart disease. CONCLUSION: The levels of FGF23, SAH, Hcy, and Homer1 tend to increase in patients with CHD compared with normal population, and the more severe the disease, the higher the levels, which has certain reference value for the clinical diagnosis of CHD and the evaluation and monitoring of the disease.


Asunto(s)
Enfermedad de la Arteria Coronaria , Hipertensión , Infarto del Miocardio , Angina Inestable , HDL-Colesterol , Enfermedad de la Arteria Coronaria/diagnóstico , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos , Proteínas de Andamiaje Homer , Homocisteína , Humanos , Hipertensión/complicaciones , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Estudios Retrospectivos
19.
BMC Cardiovasc Disord ; 22(1): 101, 2022 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-35282820

RESUMEN

BACKGROUND: To investigate the expression of serum S-adenosylhomocysteine (SAH), interleukin-1ß (IL-1ß), serum homocysteine (Hcy), tumor necrosis factor-α (TNF-α) and brain derived neurotrophic factor (BDNF) in coronary heart disease and their relationship with the degree of coronary artery disease. METHODS: A total of 132 patients with coronary heart disease (CHD) from March 2020 to April 2021 were included in this retrospective study. The experimental group was composed of CHD patients, including single-vascular group (46 cases), dual-vascular group (49 cases), and multi-vascular group (37 cases). 145 healthy subjects during the same period for physical examination constituted the control group. RESULTS: The levels of SAH, IL-1ß, Hcy, TNF-α and BDNF in single-vascular group, dual-vascular group and multi-vascular group were higher than that in control group, and the differences were statistically significant (P < 0.05). The serum levels of SAH, IL-1ß, Hcy, TNF-α and BDNF in multi-vascular group were higher than those in single-vascular group and dual-vascular group, and the serum levels of SAH, IL-1ß, Hcy, TNF-α and BDNF in dual-vascular group were higher than those in single-vascular group, with statistical significance (P < 0.05). Kendall's tau-b correlation showed that the levels of SAH, IL-1ß, Hcy, TNF-α and BDNF were positively correlated with the number of stenosis vessels (r = 0.421, 0.533, 0.301, 0.265, 0.678, P = 0.016, 0.009, 0.023, 0.036, 0.004). CONCLUSION: SAH, IL-1ß, Hcy, TNF-α and BDNF in serum of patients with CHD can be used as effective biological indicators to monitor the degree of CHD and severity of coronary stenosis.


Asunto(s)
Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Factor Neurotrófico Derivado del Encéfalo , Estenosis Coronaria/diagnóstico por imagen , Homocisteína , Humanos , Interleucina-1beta , Estudios Retrospectivos , Factor de Necrosis Tumoral alfa
20.
Dig Dis Sci ; 67(8): 3592-3600, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34705157

RESUMEN

BACKGROUND: Poor bowel preparation is commonly observed in inpatients undergoing colonoscopy, particularly those with higher risks for inadequate bowel preparation. AIMS: The objective of this study was to determine whether personalized bowel preparation regimens combined with face-to-face instruction (FFI) could improve the quality of bowel preparation for inpatient. METHODS: In this endoscopist-blinded, randomized controlled trial, 320 inpatients were enrolled and randomly allocated (1:1) to the control and intervention groups. The intervention group received FFI and personalized bowel preparation regimens, while the control group received the routine bowel preparation regimen and education. The primary outcome was adequate bowel preparation rate. Secondary outcomes included rates of procedure-related adverse events, incorrect diet restriction and laxative intake, etc. RESULTS: The adequate bowel preparation rate in the intervention group was significantly higher compared to control group [intention-to-treat (ITT) analysis: 70.0% vs 51.3%, P < 0.001; per-protocol (PP) analysis: 79.4% vs 58.6%, P < 0.001]. Bowel cleanliness was significantly improved in high-risk inpatients (ITT analysis: 65% vs 44.6%, P = 0.004; PP analysis: 73.0% vs 51.7%, P = 0.004) and in low-risk inpatients (ITT analysis: 80% vs 62.7%, P = 0.037; PP analysis: 92.3% vs 69.8%, P = 0.003). There were no significant differences between two groups regarding procedure-related adverse events. CONCLUSIONS: Personalized bowel preparation regimens combined with FFI improve the rate of adequate bowel preparation, especially for patients with high-risk factors. As such, inpatients could benefit from this novel approach for better bowel preparation to ultimately improve the quality of colonoscopies.


Asunto(s)
Colonoscopía , Pacientes Internos , Catárticos/efectos adversos , Protocolos Clínicos , Colonoscopía/métodos , Humanos , Laxativos/efectos adversos , Polietilenglicoles , Cuidados Preoperatorios/métodos
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