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1.
Am J Epidemiol ; 193(2): 296-307, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-37814392

RESUMEN

Body mass index (BMI; weight (kg)/height (m)2) is commonly used to measure general adiposity. However, evidence of its appropriateness for males and females remains inconsistent. We aimed to identify the most appropriate sex-specific power value that height should be raised to in the formula and the value that would make it achieve height independency and body fatness dependency. We randomly assigned UK Biobank participants recruited in the United Kingdom between 2006 and 2010 (n = 489,873; mean age = 56.5 years; 94.2% White) to training and testing sets (80%:20%). Using height raised to the power of -50.00 to 50.00, we identified the optimal power value that either minimized correlation with height or maximized correlation with body fat percentage, using age-adjusted correlations. The optimal power values for height were 1.77 for males and 1.39 for females. The new formulas resulted in 4.5% of females and 2.4% of males being reclassified into a different BMI category. The formulas did not show significant improvement (in terms of area under the receiver operating characteristic curve, sensitivity, and specificity) in identifying individuals with excessive body fat percentage or in predicting risk of all-cause mortality. Therefore, the conventional BMI formula is still valuable in research and disease screening for both sexes.


Asunto(s)
Bancos de Muestras Biológicas , Biobanco del Reino Unido , Masculino , Femenino , Humanos , Persona de Mediana Edad , Índice de Masa Corporal , Peso Corporal , Tejido Adiposo , Adiposidad , Estatura
2.
HIV Med ; 25(5): 529-539, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38158594

RESUMEN

INTRODUCTION: The incidence of metabolic syndrome (MetS) in people living with HIV is significantly higher than in people without HIV. MetS is not only a major driver of cardiovascular disease (CVD) but is also closely related to the development of chronic kidney disease (CKD). The aim of this study was to investigate the prevalence of and risk factors for MetS and to further understand the degree of damage to target organs. METHODS: This was a cross-sectional descriptive study conducted at Chongqing Public Health Medical Center, China. Information was collected via questionnaire survey, physical examination, and laboratory tests. We used the China Diabetes Society guidelines to define MetS. Pooled cohort equations were calculated to compare CVD risk in the next 10 years in people living with HIV aged ≥40 years with or without MetS. We used Student's t-test, the chi-squared test, Fisher's exact test, binary logistic regression, and multiple linear regression in the statistical analysis. RESULTS: The study included 979 people living with HIV, including 13 who have experienced CVD, receiving antiretroviral therapy (ART). The median age was 43.0 years, 20.9% were female, and the median ART time was 45.0 months. The prevalence of MetS was 33.9%. The components of MetS criteria were hyperglycaemia (50.4%), hypertriglyceridaemia (48.4%), hypertension (46.8%), low concentrations of high-density lipoprotein cholesterol (28.2%), and abdominal obesity (25.0%). Higher body mass index (odds ratio [OR] 1.266; 95% confidence interval [CI] 1.203-1.333), higher total cholesterol (OR 1.267; 95% CI 1.011-1.588), high alcohol consumption (OR 1.973; 95% CI 1.009-3.859), and family history of diabetes (OR 1.726; 95% CI 1.075-2.770) were independent risk factors for MetS. Compared with the non-MetS group, the MetS group had a higher rate of urine albumin (23.8% vs 14.8%, p = 0.001), and the estimated glomerular filtration rate <90 mL/min/1.73 m2 (18.37% vs. 12.8%, p = 0.020) and ß2-microglobin (p = 0.004) increased more markedly in the MetS group. Regarding the risk of developing CVD events in the next 10 years, 38.5% of those in the MetS group were at high or very high risk, which was significantly higher than in the non-MetS group (p < 0.001). In addition, age (p < 0.001) and sex (p = 0.002) are independent risk factors for developing CVD events in the next 10 years. CONCLUSIONS: The prevalence of MetS in people living with HIV on ART is high in Chongqing, China. Risk factors for the development of MetS are high alcohol consumption, family history of diabetes, higher body mass index, and higher total cholesterol levels. In addition, MetS is associated with a risk of CKD and the incidence of 10-year CVD.


Asunto(s)
Infecciones por VIH , Síndrome Metabólico , Humanos , Femenino , Masculino , Estudios Transversales , Síndrome Metabólico/epidemiología , Adulto , China/epidemiología , Persona de Mediana Edad , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Prevalencia , Factores de Riesgo , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/complicaciones , Antirretrovirales/uso terapéutico , Antirretrovirales/efectos adversos
3.
J Exp Bot ; 75(1): 258-273, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37721809

RESUMEN

Intercropping improves resource utilization. Under wide-narrow-row maize (Zea mays) intercropping, maize plants are subjected to weak unilateral illumination and exhibit high photosynthetic performance. However, the mechanism regulating photosynthesis under unilateral weak light remains unknown. We investigated the relationship between photosynthesis and sugar metabolism in maize under unilateral weak light. Our results showed that the net photosynthetic rate (Pn) of unshaded leaves increased as the level of shade on the other side increased. On the contrary, the concentration of sucrose and starch and the number of starch granules in the unshaded leaves decreased with increased shading due to the transfer of abundant C into the grains. However, sink loss with ear removal reduced the Pn of unshaded leaves. Intense unilateral shade (40% to 20% normal light), but not mild unilateral shade (60% normal light), reduced grain yield (37.6% to 54.4%, respectively). We further found that in unshaded leaves, Agpsl, Bmy, and Mexl-like expression significantly influenced sucrose and starch metabolism, while Sweet13a and Sut1 expression was crucial for sugar export. In shaded leaves, expression of Sps1, Agpsl, and Sweet13c was crucial for sugar metabolism and export. This study confirmed that unshaded leaves transported photosynthates to the ear, leading to a decrease in sugar concentration. The improvement of photosynthetic performance was associated with altered sugar transport. We propose a narrow-row spacing of 40 cm, which provides appropriate unilateral shade and limits yield reduction.


Asunto(s)
Fotosíntesis , Zea mays , Fotosíntesis/fisiología , Zea mays/fisiología , Hojas de la Planta/fisiología , Almidón , Sacarosa
4.
Prev Med ; 184: 107994, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38723779

RESUMEN

BACKGROUND: The potential health effects of taxing sugar-sweetened beverages (SSBs) has been insufficiently examined in Asian contexts. This study aimed to assess the impact of SSB taxation on the prevalence of obesity/overweight and type 2 diabetes mellitus (T2DM) in Hong Kong using a willingness-to-pay (WTP) survey and simulation analysis. METHODS: A random telephone survey was conducted with 1000 adults from May to June 2020. We used a contingent valuation approach to assess individuals' WTP for SSBs under four tax payment scenarios (5%, 10%, 40%, and 50% of the current market price). Based on the WTP, a simulation analysis was conducted to project changes in SSB purchase and associated reductions in the prevalence of obesity/overweight and T2DM over a 10-year simulation period. FINDINGS: When 5% and 10% taxation rates were introduced, approximately one-third of the population were unwilling to maintain their SSB purchase. Our simulation demonstrated a gradual decline in the prevalence of obesity/overweight and diabetes with a more pronounced decrease when higher taxation rates were introduced. 10% taxation resulted in a mean reduction of 1532.7 cases of overweight/obesity per 100 thousand population at the sixth year, while T2DM prevalence decreased by 267.1 (0.3%). CONCLUSIONS: This study underscores the effects of an SSB tax on purchase behaviors and health outcomes in an affluent Asia setting, with a more pronounced influence on adult population. These findings are expected to inform policymakers in making decisions regarding an effective and equitable tax rate on SSBs.


Asunto(s)
Diabetes Mellitus Tipo 2 , Obesidad , Sobrepeso , Bebidas Azucaradas , Impuestos , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Bebidas Azucaradas/economía , Bebidas Azucaradas/estadística & datos numéricos , Masculino , Femenino , Obesidad/epidemiología , Adulto , Sobrepeso/epidemiología , Persona de Mediana Edad , Hong Kong/epidemiología , Prevalencia , Encuestas y Cuestionarios
5.
BMC Infect Dis ; 24(1): 5, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38166781

RESUMEN

BACKGROUND: China is a country burdened with a high incidence of both tuberculosis (TB) and HIV, Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication in TB and HIV co-infected patients, but data from China are limited. Additionally, as an integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) regimen becomes the first-line treatment, concerns have arisen regarding the potential increase in the incidence of paradoxical TB-IRIS. Nevertheless, the existing data are inconclusive and contradictory. METHODS: We conducted a retrospective study at Chongqing Public Health Clinical Center from January 2018 to December 2021. We collected demographic and clinical data of HIV/TB co-infected patients who initiated ART. We described the patient characteristics, identified predictors for TB-IRIS, and determined clinical outcomes. The Statistical Package for Social Science (SPSS 25) was used to analyse the data. Continuous variables were compared using Student's t-test or rank sum test. Counting data were compared using the chi-square test or Fisher's exact test. The variables with statistical significance in the univariate analysis were added to the binary logistic regression. A p-value less than 0.05 was considered statistically significant. RESULTS: A total of 384 patients co-infected with naive HIV and pulmonary TB (PTB) who were given ATT and ART combination were included. 72 patients (18.8%) developed paradoxical TB-IRIS with a median of 15 (12, 21) days after initiating ART. Baseline age ≤ 40years, CD4 + T-cell counts ≤ 50cells/µL, HIV viral load ≥ 500,000 copies/mL were found to be significantly associated with development of paradoxical TB-IRIS. Mortality rates were similar in the TB-IRIS (n = 5, 6.9%) group and non-TB-IRIS (n = 13, 4.2%) group. Interestingly, CD4+ T-cell counts recovery post-ART was significant higher in the TB-IRIS group when compared to the non-TB-IRIS group at the end of 24 weeks (P = 0.004), as well as at 48 weeks (P = 0.015). In addition, we consider that INSTI- based ART regimen do not increased the risk of Paradoxical TB-IRIS. CONCLUSION: Paradoxical TB-IRIS, while often leading to clinical deterioration and hospitalization, is generally manageable. It appears to have a positive impact on the recovery of CD4 + T-cell counts over time. Importantly, our data suggest that INSTI-based ART regimens do not elevate the risk of TB-IRIS. Thus, paradoxical TB-IRIS should not be considered an impediment to initiating ART in adults with advanced immunodeficiency, except in the case of tuberculous meningitis (TBM).


Asunto(s)
Infecciones por VIH , Síndrome Inflamatorio de Reconstitución Inmune , Tuberculosis Meníngea , Adulto , Humanos , Estudios Retrospectivos , Síndrome Inflamatorio de Reconstitución Inmune/epidemiología , Síndrome Inflamatorio de Reconstitución Inmune/etiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Factores de Riesgo , China/epidemiología , Tuberculosis Meníngea/complicaciones
6.
Drug Resist Updat ; 71: 101011, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37865067

RESUMEN

The overexpression of the human ATP-binding cassette (ABC) transporters in cancer cells is a common mechanism involved in developing multidrug resistance (MDR). Unfortunately, there are currently no approved drugs specifically designed to treat multidrug-resistant cancers, making MDR a significant obstacle to successful chemotherapy. Despite over two decades of research, developing transporter-specific inhibitors for clinical use has proven to be a challenging endeavor. As an alternative approach, drug repurposing has gained traction as a more practical method to discover clinically effective modulators of drug transporters. This involves exploring new indications for already-approved drugs, bypassing the lengthy process of developing novel synthetic inhibitors. In this context, we will discuss the mechanisms of ABC drug transporters ABCB1 and ABCG2, their roles in cancer MDR, and the inhibitors that have been evaluated for their potential to reverse MDR mediated by these drug transporters. Our focus will be on providing an up-to-date report on approved drugs tested for their inhibitory activities against these drug efflux pumps. Lastly, we will explore the challenges and prospects of repurposing already approved medications for clinical use to overcome chemoresistance in patients with high tumor expression of ABCB1 and/or ABCG2.


Asunto(s)
Reposicionamiento de Medicamentos , Neoplasias , Humanos , Transportadoras de Casetes de Unión a ATP/genética , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Proteínas de Transporte de Membrana , Resistencia a Múltiples Medicamentos , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Proteínas de Neoplasias/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética
7.
Telemed J E Health ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38752867

RESUMEN

Objectives: Telemedicine has been widely used during the COVID-19 pandemic. Among other health care professionals, Chinese medicine practitioners (CMPs) face practical challenges in providing telemedicine consultations. This study aims to explore CMPs' experience and perceptions of telemedicine service provision before and during the pandemic. Methods: A territory-wide cross-sectional online survey was conducted in Hong Kong between April and May 2022. A structured questionnaire with open-ended questions was used to investigate the provision of and perception on telemedicine service, as well as usability of telemedicine among CMPs. Results: A total of 195 CMPs participated the survey. Before COVID-19, 42% (81/195) had been providing telemedicine services, and the proportion doubled during COVID-19. CMPs in the private sector are the main providers. Mobile apps including WhatsApp, WeChat, and Zoom were commonly used for consultations (75%, 120/161). Barriers in providing telemedicine included inability of conducting physical examination on patients (69%, 134/195), legal and ethical concerns over medical negligence (61%, 118/195), and patients' incompetence on e-literacy (50%, 98/195). Respondents urged professional and regulatory bodies to provide an explicit clinical guideline that demonstrate best practice in traditional Chinese medicine telemedicine, and to clarify legal and ethical implications of such practice. Conclusions: CMPs demonstrated their competency in telemedicine, and most of them provided telemedicine during COVID-19. Development of appropriate guidelines on the provision of telemedicine would support CMPs to continue provision after the pandemic, whereas a user-friendly and comprehensive telemedicine e-platform would enhance quality of such service. Facilitating patients with lower e-literacy to access telemedicine is key to reduce disparities.

8.
Int J Mol Sci ; 25(10)2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38791198

RESUMEN

MTX-211 is a first-in-class dual inhibitor of epidermal growth factor receptor (EGFR) and phosphoinositide-3 kinase (PI3K) signaling pathways with a compelling pharmaceutical profile and could enhance the effectiveness of mitogen-activated protein kinase kinase (MEK) inhibitor therapy in colorectal tumors with KRAS mutations. However, the specific mechanisms contributing to the acquired resistance to MTX-211 in human cancers remain elusive. Here, we discovered that the overexpression of the ATP-binding cassette (ABC) drug transporter ABCG2, a prevalent mechanism associated with multidrug resistance (MDR), could diminish the effectiveness of MTX-211 in human cancer cells. We showed that the drug efflux activity of ABCG2 substantially decreased the intracellular accumulation of MTX-211 in cancer cells. As a result, the cytotoxicity and effectiveness of MTX-211 in suppressing the activation of the EGFR and PI3K pathways were significantly attenuated in cancer cells overexpressing ABCG2. Moreover, the enhancement of the MTX-211-stimulated ATPase activity of ABCG2 and the computational molecular docking analysis illustrating the binding of MTX-211 to the substrate-binding sites of ABCG2 offered a further indication for the interaction between MTX-211 and ABCG2. In summary, our findings indicate that MTX-211 acts as a substrate for ABCG2, underscoring the involvement of ABCG2 in the emergence of resistance to MTX-211. This finding carries clinical implications and merits further exploration.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Resistencia a Antineoplásicos , Receptores ErbB , Proteínas de Neoplasias , Humanos , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inhibidores , Resistencia a Antineoplásicos/efectos de los fármacos , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/antagonistas & inhibidores , Línea Celular Tumoral , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Simulación del Acoplamiento Molecular , Transducción de Señal/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Antineoplásicos/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/patología
9.
J Sci Food Agric ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980001

RESUMEN

BACKGROUND: Relay intercropping of maize and soybean can improve land productivity. However, the mechanism behind N2O emissions in this practice remains unclear. A two-factor randomized block field trial was conducted to reveal the mechanism of N2O emissions in a full additive maize-soybean relay intercropping. Factor A was three cropping systems - that is, monoculture maize (Zea mays L.), monoculture soybean (Glycine max L. Merr.) and maize-soybean relay intercropping. Factor B was different N supply, containing no N, reduced N and conventional N. Differences in N2O emissions, soil properties, rhizosphere bacterial communities and yield advantage were evaluated. RESULTS: The land equivalent ratio was 1.55-2.44, and the cumulative N2O emission ( C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ ) was notably lower by 60.2% in intercropping than in monoculture, respectively. Reduced N declined C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ without penalty on the yield advantages. The relay intercropping shifted soil properties - for example, soil organic matter, total N, NH 4 + $$ {\mathrm{NH}}_4^{+} $$ and protease activity - and improved the soil microorganism community - for example, Proteobacteria and Acidobacteria. Intercropping reduced C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ by directly suppressing nirS- and amoA-regulated N2O generation during soil N cycling, or nirS- and amoA-mediated soil properties shifted to reduce C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ indirectly. Reduced N directly reduced C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ by decreasing soil N content and reducing soil microorganism activities to alleviate N2O produced in soil N cycling. CONCLUSION: Conducting a full additive maize-soybean relay intercropping with reduced nitrogen supply provides a way to alleviate N2O emissions without the penalty on the yield advantage by changing rhizosphere bacterial communities and soil N cycling. © 2024 Society of Chemical Industry.

10.
BMC Plant Biol ; 23(1): 438, 2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37726682

RESUMEN

Intercropping can obtain yield advantages, but the mechanism of yield advantages of maize-legume intercropping is still unclear. Then, we explored the effects of cropping systems and N input on yield advantages in a two-year experiment. Cropping systems included monoculture maize (Zea mays L.) (MM), monoculture soybean (Glycine max L. Merr.) (MS), monoculture peanut (Arachis hypogaea L.) (MP), maize-soybean substitutive relay intercropping (IMS), and maize-peanut substitutive strip intercropping (IMP). N input included without N (N0) and N addition (N1). Results showed that maize's leaf area index was 31.0% and 34.6% higher in IMS and IMP than in MM. The specific leaf weight and chlorophyll a (chl a) of maize were notably higher by 8.0% and 18.8% in IMS, 3.1%, and 18.6% in IMP compared with MM. Finally, N addition resulted in a higher thousand kernels weight of maize in IMS and IMP than that in MM. More dry matter accumulated and partitioned to the grain, maize's averaged partial land equivalent ratio and the net effect were 0.76 and 2.75 t ha-1 in IMS, 0.78 and 2.83 t ha-1 in IMP. The leaf area index and specific leaf weight of intercropped soybean were 16.8% and 26% higher than MS. Although soybean suffers from shade during coexistence, recovered growth strengthens leaf functional traits and increases dry matter accumulation. The averaged partial land equivalent ratio and the net effect of intercropped soybean were 0.76 and 0.47 t ha-1. The leaf area index and specific leaf weight of peanuts in IMP were 69.1% and 14.4% lower than in the MP. The chlorophyll a and chlorophyll b of peanut in MP were 17.0% and 24.4% higher than in IMP. A less dry matter was partitioned to the grain for intercropped peanut. The averaged pLER and NE of intercropped peanuts were 0.26 and -0.55 t ha-1. In conclusion, the strengthened leaf functional traits promote dry matter accumulation, maize-soybean relay intercropping obtained a win-win yield advantage, and maize-peanut strip intercropping achieved a trade-off yield advantage.


Asunto(s)
Fabaceae , Zea mays , Clorofila A , Verduras , Glycine max , Arachis , Hojas de la Planta , Grano Comestible
11.
PLoS Comput Biol ; 18(6): e1010281, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35759509

RESUMEN

In the context of infectious disease transmission, high heterogeneity in individual infectiousness indicates that a few index cases can generate large numbers of secondary cases, a phenomenon commonly known as superspreading. The potential of disease superspreading can be characterized by describing the distribution of secondary cases (of each seed case) as a negative binomial (NB) distribution with the dispersion parameter, k. Based on the feature of NB distribution, there must be a proportion of individuals with individual reproduction number of almost 0, which appears restricted and unrealistic. To overcome this limitation, we generalized the compound structure of a Poisson rate and included an additional parameter, and divided the reproduction number into independent and additive fixed and variable components. Then, the secondary cases followed a Delaporte distribution. We demonstrated that the Delaporte distribution was important for understanding the characteristics of disease transmission, which generated new insights distinct from the NB model. By using real-world dataset, the Delaporte distribution provides improvements in describing the distributions of COVID-19 and SARS cases compared to the NB distribution. The model selection yielded increasing statistical power with larger sample sizes as well as conservative type I error in detecting the improvement in fitting with the likelihood ratio (LR) test. Numerical simulation revealed that the control strategy-making process may benefit from monitoring the transmission characteristics under the Delaporte framework. Our findings highlighted that for the COVID-19 pandemic, population-wide interventions may control disease transmission on a general scale before recommending the high-risk-specific control strategies.


Asunto(s)
COVID-19 , Enfermedades Transmisibles , COVID-19/epidemiología , Enfermedades Transmisibles/epidemiología , Humanos , Funciones de Verosimilitud , Modelos Estadísticos , Pandemias/prevención & control
12.
Int J Mol Sci ; 24(18)2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37762275

RESUMEN

ATP-binding cassette transporters, including ABCB1 (P-glycoprotein) and ABCG2 (BCRP/MXR/ABCP), are pivotal in multidrug resistance (MDR) development in cancer patients undergoing conventional chemotherapy. The absence of approved therapeutic agents for multidrug-resistant cancers presents a significant challenge in effectively treating cancer. Researchers propose repurposing existing drugs to sensitize multidrug-resistant cancer cells, which overexpress ABCB1 or ABCG2, to conventional anticancer drugs. The goal of this study is to assess whether furmonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor overcomes drug resistance mediated by ABCB1 and ABCG2 transporters. Furmonertinib stands out due to its ability to inhibit drug transport without affecting protein expression. The discovery of this characteristic was validated through ATPase assays, which revealed interactions between furmonertinib and ABCB1/ABCG2. Additionally, in silico docking of furmonertinib offered insights into potential interaction sites within the drug-binding pockets of ABCB1 and ABCG2, providing a better understanding of the underlying mechanisms responsible for the reversal of MDR by this repurposed drug. Given the encouraging results, we propose that furmonertinib should be explored as a potential candidate for combination therapy in patients with tumors that have high levels of ABCB1 and/or ABCG2. This combination therapy holds the potential to enhance the effectiveness of conventional anticancer drugs and presents a promising strategy for overcoming MDR in cancer treatment.

13.
BMC Infect Dis ; 22(1): 677, 2022 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-35941618

RESUMEN

BACKGROUND: The most appropriate alternative to induction therapy for HIV-associated cryptococcal meningitis (CM) remains unclear when standard treatment is unavailable, inaccessible, intolerable, or ineffective. METHODS: A prospective, multi-centre cohort study was conducted to analyze the data of 156 HIV-infected patients with CM who were treated with amphotericin B deoxycholate (AmB-D) + flucytosine (5FC), voriconazole (VCZ) + 5FC, or AmB-D + Fluconazole (Flu) as induction regimens. Clinical efficacy, cumulative mortality, and adverse effects were compared among the three treatment groups. RESULTS: Fewer deaths occurred by week 4 and week 10 among patients receiving AmB-D + 5FC than among those receiving AmB-D + Flu [4 (5.1%) vs. 8 (16.0%) deaths by week 4; hazard ratio, 1.8; 95% confidence interval [CI], 1.0 to 3.3; p = 0.039; and 8 (10.3%) vs. 14 (28.0%) deaths by week 10; hazard ratio, 1.8; 95% CI, 1.1 to 2.7; p = 0.008, respectively]. AmB-D plus 5FC was found to result in significantly higher rates of cerebrospinal fluid (CSF) culture sterility (57.6% vs. 34% by week 2; 87.9% vs. 70% by week 10; p < 0.05 for both comparisons). However, the differences in CSF culture sterility and mortality between the VCZ + 5FC group and the AmB-D + 5FC group were not statistically significant. VCZ plus 5FC had a significantly advantageous effect on the incidence of new AIDS-defining illness and length of hospital stay, compared with AmB-D plus 5FC. Laboratory adverse events (grade 3 or 4), such as severe anemia, were less frequent with VCZ + 5FC use than with AmB-D combined with 5FC or Flu use. CONCLUSION: Our results suggest that AmB-D combined with 5FC remains the more efficacious induction regimen compared to AmB-D plus Flu, and that VCZ + 5FC might be a potential alternative when the standard regimen is not readily available, accessible, tolerated, or effective. CLINICAL TRIALS: Registration number, ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 .


Asunto(s)
Infecciones por VIH , Infertilidad , Meningitis Criptocócica , Anfotericina B , Antifúngicos/efectos adversos , Estudios de Cohortes , Ácido Desoxicólico , Combinación de Medicamentos , Quimioterapia Combinada , Fluconazol/efectos adversos , Flucitosina/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Infertilidad/inducido químicamente , Infertilidad/tratamiento farmacológico , Estudios Prospectivos , Voriconazol/uso terapéutico
14.
BMC Anesthesiol ; 22(1): 358, 2022 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-36424549

RESUMEN

BACKGROUND: This study aimed to translate the French version of a perioperative satisfaction questionnaire (EVAN-G) scale, a validated questionnaire for assessing perioperative patient satisfaction, into a Chinese version and validate it in Chinese-speaking patients. METHODS: We developed the Chinese version of the EVAN-G (EVAN-GC) scale based on the original French version of the EVAN-G. The EVAN-GC scale, the Short version of the Spielberger State-Trait Anxiety Inventory (S-STAI), and the McGill pain questionnaire (MGPQ) were administered on the WeChat mini program. We invited patients to complete these questionnaires within 4 to 24 h after surgery. The psychometric validation of the EVAN-GC scale included validity, reliability, and acceptability. RESULTS: Among 220 patients, 217 (98.6%) completed the EVAN-GC scale after surgery. The item-internal consistency revealed good construct validity. Compared with the total scores of the S-STAI and MGPQ, the EVAN-GC scale showed excellent convergent validity (ρ = - 0.32, P < 0.001; ρ = - 0.29, P < 0.001). The EVAN-GC scale could differentiate between groups, which showed good discriminate validity. The Cronbach's alpha coefficient (0.85) of the translated scale demonstrated satisfactory internal consistency reliability, and a 36-patient subsample retest evidenced good test-retest reliability (ρ = 0.82, P < 0.001). In addition, the median [interquartile range] time of completing the EVAN-GC scale was 3.7 [2.9-4.9] min. CONCLUSIONS: The EVAN-GC scale has good psychometric properties similar to those of the original French version. The EVAN-GC scale is a valid and reliable measurement to assess patient satisfaction in Chinese-speaking patients. TRIAL REGISTRATION: The Chinese Clinical Trial Registry, ChiCTR2100049555.


Asunto(s)
Pueblo Asiatico , Satisfacción del Paciente , Humanos , Reproducibilidad de los Resultados , China
15.
BMC Health Serv Res ; 22(1): 163, 2022 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-35135539

RESUMEN

BACKGROUND: China implemented a universal two-child policy in 2015. It is important to understand infants' medical utilization in the context of this policy to inform health policies and resource allocation. METHODS: This study utilized a 20% random sample of administrative data from China's Urban and Rural Basic Medical Insurance (URBMI) in one of the largest southern Chinese cities from January 2015 to June 2018. Ordinary least squares models were used to estimate changes in inpatient admission rates and costs for infants between 0 and 6 months old after the implementation of China's universal two-child policy. RESULTS: The overall inpatient admission rate was 27.2% in 2015 and 31.3% in 2017. Compared with 2015, there was an increase in inpatient admission rates for infants 1 month old or younger (coef = 0.038, 95% CI = 0.029 to 0.047, p < .001) and infants 6 months old or younger (coef = 0.041, 95% CI = 0.030 to 0.052, p < .001) in 2017. The increase was larger for male infants than for female ones. The average inpatient admission cost was 8412.3 RMB ($1320.61) (SD = 15,088.2). There was no increase in inpatient admission costs overall. The average length of hospital stay was 7.3 days, the probability of going to a tertiary hospital was 76.2%, and the share of out-of-pocket costs was 53.0% for all diseases. CONCLUSION: After the implementation of the universal two-child policy in China, there was a significant increase in inpatient admission rates, especially for male infants. The overall associated costs did not change, but the increase in admission rates caused additional economic burdens for families and for social health insurance. Understanding the healthcare utilization of infants in the universal two-child period can provide insight for healthcare resource allocation in a time of dramatic changes in population policy.


Asunto(s)
Pacientes Internos , Seguro de Salud , China , Femenino , Política de Salud , Humanos , Lactante , Recién Nacido , Masculino , Población Urbana
16.
BMC Med Educ ; 22(1): 157, 2022 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-35260163

RESUMEN

BACKGROUND: Health technology assessment (HTA) has become essential in many countries over the past few years, and the demand for HTA professionals has increased in academia, governments, and industries. This study aimed to examine which courses are most important and which training activities are most helpful for the development of HTA proficiency as perceived by HTA experts. METHODS: The survey questionnaire was developed by literature review and expert opinion. Convenience sampling was used to survey HTA experts from the industrial sector, academic/research units, and government/independent assessment organizations using an online survey tool, SurveyCake. We collected respondents' demographic information and asked them to assess the importance of each course included in an HTA program on a 5-point Likert Scale (1 = least important; 5 = highly important). In addition, respondents were asked to assess the extent to which various activities are helpful for HTA proficiency development. RESULTS: A total of 158 domestic and overseas experts in HTA-related fields were invited to participate in the survey and 68 completed the questionnaire. Among the respondents, the majority were female (57.4%) and working in academia (44.1%). The mean ± standard deviation of respondents' age and number of years spent in HTA-related fields were 43.2 ± 11.0 years and 11.3 ± 9.9 years, respectively. The course that was rated the most important was "Pharmacoeconomics/Cost-effectiveness analysis" with a score of 4.8 ± 0.4 points, followed by "Health economics" at 4.7 ± 0.7 points. Moreover, internships at HTA-related institutions were perceived to be the most helpful training activity for HTA proficiency development. CONCLUSIONS: Our study findings provide a better understanding of the requirements for developing HTA proficiency and can serve as a reference for the modification of current HTA education and training programs.


Asunto(s)
Tecnología Biomédica , Evaluación de la Tecnología Biomédica , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Proyectos de Investigación , Encuestas y Cuestionarios
17.
Int J Mol Sci ; 23(21)2022 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-36361555

RESUMEN

Hydroxygenkwanin, a flavonoid isolated from the leaves of the Daphne genkwa plant, is known to have pharmacological properties; however, its modulatory effect on multidrug resistance, which is (MDR) mediated by ATP-binding cassette (ABC) drug transporters, has not been investigated. In this study, we examine the interaction between hydroxygenkwanin, ABCB1, and ABCG2, which are two of the most well-characterized ABC transporters known to contribute to clinical MDR in cancer patients. Hydroxygenkwanin is not an efflux substrate of either ABCB1 or ABCG2. We discovered that, in a concentration-dependent manner, hydroxygenkwanin significantly reverses ABCG2-mediated resistance to multiple cytotoxic anticancer drugs in ABCG2-overexpressing multidrug-resistant cancer cells. Although it inhibited the drug transport function of ABCG2, it had no significant effect on the protein expression of this transporter in cancer cells. Experimental data showing that hydroxygenkwanin stimulates the ATPase activity of ABCG2, and in silico docking analysis of hydroxygenkwanin binding to the inward-open conformation of human ABCG2, further indicate that hydroxygenkwanin sensitizes ABCG2-overexpressing cancer cells by binding to the substrate-binding pocket of ABCG2 and attenuating the transport function of ABCG2. This study demonstrates the potential use of hydroxygenkwanin as an effective inhibitor of ABCG2 in drug combination therapy trials for patients with tumors expressing higher levels of ABCG2.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Resistencia a Múltiples Medicamentos , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Resistencia a Antineoplásicos , Proteínas de Neoplasias/metabolismo , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/química , Flavonoides/farmacología , Transportadoras de Casetes de Unión a ATP/metabolismo , Neoplasias/tratamiento farmacológico
18.
Plant Cell Environ ; 44(8): 2536-2550, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34118074

RESUMEN

Mildew severely reduces soybean yield and quality, and pods are the first line of defence against pathogens. Maize-soybean intercropping (MSI) reduces mildew incidence on soybean pods; however, the mechanism remains unclear. Changing light (CL) from maize shading is the most important environmental feature in MSI. We hypothesized that CL affects isoflavone accumulation in soybean pods, affecting their disease resistance. In the present study, shading treatments were applied to soybean plants during different developmental stages according to various CL environments under MSI. Chlorophyll fluorescence imaging (CFI) and classical evaluation methods confirmed that CL, especially vegetative stage shading (VS), enhanced pod resistance to mildew. Further metabolomic analyses and exogenous jasmonic acid (JA) and biosynthesis inhibitor experiments revealed the important relationship between JA and isoflavone biosynthesis, which had a synergistic effect on the enhanced resistance of CL-treated pods to mildew. VS promoted the biosynthesis and accumulation of constitutive isoflavones upstream of the isoflavone pathway, such as aglycones and glycosides, in soybean pods. When mildew infects pods, endogenous JA signalling stimulated the biosynthesis of downstream inducible malonyl isoflavone (MIF) and glyceollin to improve pod resistance.


Asunto(s)
Glycine max/metabolismo , Glycine max/microbiología , Isoflavonas/biosíntesis , Enfermedades de las Plantas/microbiología , Acetatos/farmacología , Cromatografía Líquida de Alta Presión , Ciclopentanos/metabolismo , Ciclopentanos/farmacología , Resistencia a la Enfermedad/efectos de los fármacos , Resistencia a la Enfermedad/fisiología , Fusarium/patogenicidad , Regulación de la Expresión Génica de las Plantas , Isoflavonas/análisis , Luz , Inhibidores de la Lipooxigenasa/farmacología , Metabolómica/métodos , Oxilipinas/metabolismo , Oxilipinas/farmacología , Pirazoles/farmacología , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas de Soja/genética , Glycine max/efectos de los fármacos , Glycine max/genética , Espectrometría de Masas en Tándem
19.
Int J Equity Health ; 20(1): 145, 2021 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-34158068

RESUMEN

BACKGROUND: Most existing research on rural-urban health inequalities focuses on disparities in service access and health outcomes based on region. This paper examines rural-urban disparities in maternal healthcare utilization and delivery modes based on household registration (hukou) status to understand the role of state institutions in producing healthcare disparities in China. METHODS: Utilizing administrative data from the Public Maternal Health Insurance scheme, we analyzed 54,733 live births in City A (2015-2019) and 25,849 live births in City B (2018-2019) in Guangdong Province in China. We constructed regression models using hukou status (rural versus urban) as the explanatory variable. RESULTS: While there is no statistically significant difference in rural and urban mothers' probability of obtaining the minimum recommended number of prenatal care checkups in City A (OR = 0.990 [0.950, 1.032]), mothers with rural hukou status have a lower probability of obtaining the minimum recommended number of visits in City B than their counterparts with urban hukou (OR = 0.781 [0.740, 0.825]). The probability of delivering in tertiary hospital is lower among mothers with rural hukou than among those with urban hukou in both cities (City A: OR = 0.734 [0.701, 0.769]; City B: OR = 0.336 [0.319, 0.354]). Mothers with rural hukou are more likely to have a Cesarean section than those with urban hukou in both cities (City A: OR = 1.065 [1.027, 1.104]; City B: OR = 1.127 [1.069, 1.189]). Compared with mothers with urban hukou, mothers with rural hukou incurred 4 % (95 % CI [-0.046, -0.033]) and 9.4 % (95 % CI [-0.120, -0.068]) less in total medical costs for those who delivered via Cesarean section and 7.8 % (95 % CI [-0.085, -0.071]) and 19.9 % (95 % CI [-0.221, -0.177]) less for those who delivered via natural delivery in City A and City B, respectively. CONCLUSIONS: Rural hukou status is associated with younger age, no difference or lower probability of having a minimum number of prenatal checkups, higher likelihood of delivering in nontertiary hospitals, increased Cesarean delivery rates, and lower medical cost for delivery in these two Chinese cities. Evaluating how hukou status influences maternal healthcare in Chinese cities is important for devising targeted public policies to promote more equitable maternal health services.


Asunto(s)
Disparidades en Atención de Salud , Servicios de Salud Materna , Cesárea , China , Ciudades , Femenino , Humanos , Embarazo , Población Rural , Población Urbana
20.
J Nat Prod ; 84(9): 2544-2553, 2021 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-34496204

RESUMEN

Elevated expression of the ATP-binding cassette (ABC) drug transporter ABCG2 in cancer cells contributes to the development of the multidrug resistance phenotype in patients with advanced non-small-cell lung cancer (NSCLC). Due to the lack of U.S. Food and Drug Administration (FDA)-approved synthetic inhibitors of ABCG2, significant efforts have been invested in discovering bioactive compounds of plant origin that are capable of reversing ABCG2-mediated multidrug resistance in cancer cells. Sophoraflavanone G (SFG), a phytoncide isolated from the plant species Sophora flavescens, is known to possess a wide spectrum of pharmacological activities, including antibacterial, anti-inflammatory, antimalarial, and antiproliferative effects. In the present study, the chemosensitizing effect of SFG in ABCG2-overexpressing NSCLC cells was investigated. Experimental results demonstrate that at subtoxic concentrations SFG significantly reversed ABCG2-mediated multidrug resistance in a concentration-dependent manner. Additional biochemical data and in silico docking analysis of SFG to the inward-open conformation of human ABCG2 indicate that SFG inhibited the drug transport function of ABCG2 by interacting with residues within the transmembrane substrate-binding pocket of ABCG2. Collectively, these findings provide evidence that SFG has the potential to be further tested as an effective inhibitor of ABCG2 to improve the efficacy of therapeutic drugs in patients with advanced NSCLC.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Flavanonas/farmacología , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Línea Celular Tumoral , Humanos , Simulación del Acoplamiento Molecular , Proteínas de Neoplasias
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