RESUMO
BACKGROUND: Transient synovitis of the hip is the most common cause of limping in paediatric emergency departments. There is no consensus regarding routine follow-up after hip synovitis among children, and there are no standardized criteria for selecting cases that warrant follow-up due to persistent or recurring symptoms to rule out the possibility of Legg-Calvé-Perthes disease. Delayed treatment of Legg-Calvé-Perthes disease may increase the risk of developing early secondary coxarthrosis. Understanding the prevalence of Legg-Calvé-Perthes disease among paediatric patients with transient synovitis of the hip is of paramount importance and could empower both parents and paediatricians to make well-informed decisions when selecting follow-up care for children, thus ensuring that no cases of Legg-Calvé-Perthes disease are missed among diagnosis paediatric patients with transient synovitis of the hip. The aim of this review was to estimate the prevalence of Legg-Calvé-Perthes disease among paediatric patients with transient synovitis of the hip. METHODS: This study was conducted in strict accordance with the PRISMA guidelines and was registered with PROSPERO. The PubMed, Embase, and Cochrane Library databases were comprehensively searched up to July 2024 to identify relevant studies. The inclusion criteria were as follows: patients diagnosed with transient synovitis of the hip; patients aged up to 18 years; and studies with a minimum of 10 cases of paediatric transient synovitis of the hip. To pool the prevalence rates from individual studies, we utilized a random-effects meta-analysis. To assess the quality of the included studies in detail, we employed the Joanna Briggs Institute's quality assessment checklist. RESULTS: A total of 19 studies were ultimately included for the final analysis, with 2,617 paediatric cases of transient synovitis of the hip. The results of meta-analysis revealed that the pooled prevalence estimate of Legg-Calvé-Perthes disease among all paediatric patients with transient synovitis of the hip was 2.7% (95% CI 1.4-5.1). Significant heterogeneity was observed across the studies included in this analysis (I2 = 79.990%; P = 0.000). The pooled prevalence estimate of Legg-Calvé-Perthes disease among paediatric patients with recurrent or persistent transient synovitis of the hip was 36.3% (95% CI 21.6-54.2). Significant heterogeneity was also observed across the studies included in this analysis (I2 = 51.519%; P = 0.036). Furthermore, the follow-up period varied from 6 weeks to 24 months. The primary diagnostic imaging modality utilized for identifying Perthes disease was X-ray. CONCLUSION: Our study revealed that among paediatric patients with transient synovitis of the hip, routine X-ray follow-up of the hips after 6 weeks to rule out Legg-Calvé-Perthes disease is warranted only in patients who exhibit persistent or recurrent symptoms.
Assuntos
Doença de Legg-Calve-Perthes , Sinovite , Doença de Legg-Calve-Perthes/epidemiologia , Humanos , Prevalência , Criança , Sinovite/epidemiologia , Pré-Escolar , Feminino , Adolescente , Masculino , Articulação do QuadrilRESUMO
Heterosis is the phenomenon that the hybrid offspring outperform two-parent population. Hybridisation has been widely used in plant and animal production as it effectively improves the growth and developmental performance, reproductive performance and disease resistance of the offspring. Hybridization can effectively improve the growth and development performance, reproductive performance and disease resistance of offspring, so it is widely used in animal and plant production. Researchers have used cross-breeding techniques to cultivate excellent new agricultural and animal husbandry strains and supporting lines such as super-excellent Chaoyou 1000 hybrid rice, Xiaoyan No.6 hybrid wheat, Dumeng sheep, and Shanxia black pigs. However, there are still some urgent problems in the current hybrid dominance research: the existing hybrid dominance theory can only partially explain the phenomenon of plant and animal hybrid dominance, and the theory of animal hybrid dominance is less researched, and the accuracy of the existing hybrid dominance prediction methods is limited. China is the world's largest pork production and consumption country. Heterosis can effectively improve the production performance of pigs, and its application in the pig industry has important economic and research value. However, the existing research on pig hybrid production is in its infancy and needs to be further studied. In this review, we summarize the existing heterosis theory, heterosis prediction methods, and their application in pig production, to provide a reference for the application of heterosis in pig breeding.
Assuntos
Vigor Híbrido , Animais , Suínos/genética , Hibridização Genética , Criação de Animais Domésticos/métodos , Cruzamento/métodosRESUMO
Objective: To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease (NAFLD). Methods: Literature from Web of Science, PubMed, and Embase between January 1980 and September 2022 was systematically searched. Meta-analyses of the genetic variants were conducted using at least five data sources. The epidemiologic credibility of the significant associations was graded using the Venice criteria. Results: Based on literature screening, 399 eligible studies were included, comprising 381 candidate gene association, 16 genome-wide association, and 2 whole-exome sequencing studies. We identified 465 genetic variants in 173 genes in candidate gene association studies, and 25 genetic variants in 17 genes were included in the meta-analysis. The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD, with cumulative epidemiological evidence of an association graded as strong for two variants in two genes ( HFE, TNF), moderate for four variants in three genes ( TM6SF2, GCKR, and ADIPOQ), and weak for five variants in five genes ( MBOAT7, PEMT, PNPLA3, LEPR, and MTHFR). Conclusion: This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD, which may help understand the genetic architecture of NAFLD risk.
Assuntos
Predisposição Genética para Doença , Variação Genética , Hepatopatia Gordurosa não Alcoólica , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Humanos , Estudo de Associação Genômica AmplaRESUMO
PURPOSE: This study aims to explore the adverse impacts of abusive supervision on helping behaviors among employees, as mediating by intention to leave and moderating by Islamic work ethics (IWE). DESIGN/METHODOLOGY/APPROACH: A quantitative approach was employed, and the sample consisted of 283 nurses working in various public sector hospitals in Pakistan. The data analysis was conducted using SPSS and AMOS with the PROCESS macro. FINDINGS: The results suggest that abusive supervision diminishes helping behavior among nurses. Additionally, the study reveals that intention to leave mediates the relationship of abusive supervision and nurses' helping behavior. Moreover, the introduction of IWE as a boundary condition reveals that the mediated link is weaker when IWE is higher, and vice versa. PRACTICAL IMPLICATIONS: This study provides valuable insights for hospital authorities to develop intervention strategies and policies aimed at reducing abusive supervision in hospitals. Hospital management should also be aware of the detrimental effects of abusive supervision on nurses' helping behaviors, which can be mitigated by promoting ethical values aligned with IWE. ORIGINALITY/VALUE: This study makes a valuable contribution to the limited research on the link between abusive supervision and helping behaviors in hospital settings. It offers new perspectives by incorporating the Conservation of Resources theory, particularly within the healthcare sector. Furthermore, this research expands the current knowledge by investigating the mediating influence of intention to leave and the moderating effect of IWE in mitigating the adverse impact of abusive supervision on nurses' helping behavior in Pakistan's public sector hospitals.
Assuntos
Comportamento de Ajuda , Recursos Humanos de Enfermagem Hospitalar , Humanos , Paquistão , Feminino , Adulto , Recursos Humanos de Enfermagem Hospitalar/psicologia , Masculino , Inquéritos e Questionários , Hospitais PúblicosRESUMO
BACKGROUND: Significant efforts have been devoted to assess the effects of the poly-gamma-glutamic acid (γ-PGA) on crop growth, yield and quality, soil water retention and fertilizer use efficiency. However, few studies have evaluated the effects of γ-PGA on greenhouse gas (GHG) emissions and grain yield from paddy fields with different rice varieties. METHODS: In the present study, a split-plot field experiment was performed to comprehensively evaluate the effects of γ-PGA concentrations (i.e., no application [P0] and 25.0 kg ha-1 of γ-PGA fermentation solution [P1]) and rice varieties (i.e., conventional rice [Huanghuazhan, H], red rice [Gangteyou 8024, R] and black rice [Black indica rice, B]) on the grain yield, GHG emissions, global warming potential (GWP), greenhouse gas intensity (GHGI), net ecosystem economic profit (NEEP) and carbon footprint (CF) during 2022 and 2023 rice-growing seasons in central China. RESULTS: Application of γ-PGA significantly affected the GHGs emissions, NEEP and CF. Compared with P0 treatments, P1 treatments significantly increased the NEEP by 1.2-11.2 %, and decreased the GWP by 12.9-35.4 %, the GHGI by 16.5-35.9 % and the CF by 13.8-26.2 % in 2022-2023. Application of γ-PGA showed a tendency to increase the yield. Under γ-PGA application condition, R treatment exhibited the lowest GWP, GHGI and CF, and the highest yield and NEEP compared with B and H treatments. CONCLUSION: Our results suggest that γ-PGA application is an ecological agricultural management to increase rice yield, reduce greenhouse gas emission and increase economic benefit, and its advantage is more significant for red rice than for other rice varieties.
Assuntos
Gases de Efeito Estufa , Oryza , Oryza/crescimento & desenvolvimento , Gases de Efeito Estufa/análise , China , Ácido Poliglutâmico/análogos & derivados , Agricultura/métodos , Fertilizantes , Grão Comestível/crescimento & desenvolvimento , Aquecimento GlobalRESUMO
OBJECTIVES: To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation (MPR), and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population. METHODS: The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected. Volume reconstruction (VR) and MPR were performed on the skull, and 160 cranial suture tomography images were generated for each sample. Then the MPR images of cranial sutures were scored according to the closure grading criteria, and the mean closure grades of sagittal suture, coronal sutures (both left and right) and lambdoid sutures (both left and right) were calculated respectively. Finally taking the above grades as independent variables, the linear regression model and four machine learning models for age estimation (gradient boosting regression, support vector regression, decision tree regression and Bayesian ridge regression) were established for northern Chinese Han adults age estimation. The accuracy of each model was evaluated. RESULTS: Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest. All four machine learning models had higher age estimation accuracy than linear regression model. The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years. CONCLUSIONS: The combination of skull CT-MPR and machine learning model can be used for age estimation in northern Chinese Han adults, but it is still necessary to combine with other adult age estimation indicators in forensic practice.
Assuntos
Determinação da Idade pelo Esqueleto , Suturas Cranianas , Aprendizado de Máquina , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Determinação da Idade pelo Esqueleto/métodos , Teorema de Bayes , China/etnologia , Suturas Cranianas/diagnóstico por imagem , População do Leste Asiático , Etnicidade , Antropologia Forense/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional , Modelos Lineares , Estudos Retrospectivos , Crânio/diagnóstico por imagemRESUMO
This paper presents a frequency selective surface (FSS) with a wideband second-order bandpass response in the dual-band of microwave and millimeter wave. The overall structure consists of three layers of metal pattern and two layers of thin dielectric substrate. The top and bottom metal layers have capacitive patches with integrated curled Jerusalem cross slot resonators, while the intermediate metal layer has an inductive grid structure with cross-shaped slot resonators. The incorporated slot resonators play a pivotal role in achieving the desired transmission poles or zeros, which enable a wideband second-order filtering response in the dual-band and a quick roll-off at the passband edges, increasing the efficacy of electromagnetic shielding. To fully investigate the structure's frequency response, an equivalent circuit model of the structure is created, spanning the complete frequency range of 5-50 GHz. Physical samples are created and measured to confirm the suggested approach's efficacy. The passband center frequencies of the FSS are found at f1 = 19.42 GHz and f2 = 42.78 GHz, and the - 3 dB bandwidth is 4.34 GHz (17.25-21.59 GHz) and 8.54 GHz (38.51-47.05 GHz), respectively. The simulation results align well with the experimental data. The transmission response rapidly transitions from the passband to the stopband at the passband boundaries.
RESUMO
BACKGROUND: There are numerous publications on inpatient medication errors. However, little focus is given to medication errors that occur at home. AIMS: To describe and analyse the types of medication errors among community-dwelling patients following their discharge from an acute care hospital in Singapore. METHOD: This is a retrospective review of a 'good catch' reporting system from December 2018 to March 2022. Medication-related errors were extracted and analysed. FINDINGS: A total of 73 reported medication-related error incidents were reviewed. The mean age of the patients was 78 years old (SD=9). Most patients managed their medications independently at home (45.2%, n=33). The majority of medications involved were cardiovascular medications (51.5%, n=50). Incorrect dosing (41.1%, n=39) was the most common medication error reported. Poor understanding of medication usage (35.6%, n=26) and lack of awareness of medication changes after discharge (24.7%, n=18) were the primary causes of the errors. CONCLUSION: This study's findings provide valuable insights into reducing medication errors at home. More attention must be given to post-discharge care, especially to preventable medication errors. Medication administration and management education can be emphasised using teach-back methods.
Assuntos
Erros de Medicação , Segurança do Paciente , Humanos , Erros de Medicação/prevenção & controle , Idoso , Feminino , Estudos Retrospectivos , Masculino , Singapura , Idoso de 80 Anos ou mais , Alta do Paciente , Pessoa de Meia-Idade , Vida IndependenteRESUMO
This work presents a novel tri-band bandpass frequency selective surface (FSS) that achieves high-order filtering responses in different frequency bands by means of a complementary structure. The proposed FSS is composed of three metal periodic arrays, which are separated by multilayer dielectric substrates. The gridded-double convoluted loop (G-DCL) structure, which is the middle layer structure, is a hybrid resonator that generates different resonant frequencies. The top and bottom layer structures are designed as complementary structures to the middle layer. To accurately describe the frequency responses, an equivalent circuit model (ECM) has been constructed over the entire band from 0 to 16 GHz. The results of the simulation indicate that the developed FSS can generate three pass-bands operating at 3.79 GHz, 8.34 GHz, and 12.52 GHz, respectively, and - 3 dB fractional bandwidths are 52.8%, 13.7%, and 19.7%. The transmission responses at the edges of each passband show a quick roll-off from the passband to the stopband, and there is significant out-of-band suppression between adjacent passbands. Moreover, the FSS maintains excellent angular and polarization stability within a 50° range. For verification, the tri-band FSS has been fabricated and tested. The experimental results match the simulation results, validating the accuracy of the FSS design.
RESUMO
The generation of ultra-low-noise microwave and mmWave in miniaturized, chip-based platforms can transform communication, radar and sensing systems1-3. Optical frequency division that leverages optical references and optical frequency combs has emerged as a powerful technique to generate microwaves with superior spectral purity than any other approaches4-7. Here we demonstrate a miniaturized optical frequency division system that can potentially transfer the approach to a complementary metal-oxide-semiconductor-compatible integrated photonic platform. Phase stability is provided by a large mode volume, planar-waveguide-based optical reference coil cavity8,9 and is divided down from optical to mmWave frequency by using soliton microcombs generated in a waveguide-coupled microresonator10-12. Besides achieving record-low phase noise for integrated photonic mmWave oscillators, these devices can be heterogeneously integrated with semiconductor lasers, amplifiers and photodiodes, holding the potential of large-volume, low-cost manufacturing for fundamental and mass-market applications13.
RESUMO
NMR chemical shifts provide a sensitive probe of protein structure and dynamics but remain challenging to predict and interpret. We examine the effect of protein conformational distributions on 15N chemical shifts for dihydrofolate reductase (DHFR), comparing QM/MM predicted shifts with experimental shifts in solution as well as frozen distributions. Representative snapshots from MD trajectories exhibit variation in predicted 15N chemical shifts of up to 25 ppm. The average over the fluctuations is in significantly better agreement with room temperature solution experimental values than the prediction for any single optimal conformations. Meanwhile, solid-state NMR (SSNMR) measurements of frozen solutions at 105 K exhibit broad lines whose widths agree well with the widths of distributions of predicted shifts for samples from the trajectory. The backbone torsion angle ψi-1 varies over 60° on the picosecond time scale, compensated by φi. These fluctuations can explain much of the shift variation.
Assuntos
Imageamento por Ressonância Magnética , Proteínas , Temperatura , Conformação Proteica , Espectroscopia de Ressonância Magnética , Proteínas/química , Ressonância Magnética Nuclear BiomolecularRESUMO
While low-temperature Nuclear Magnetic Resonance (NMR) holds great promise for the analysis of unstable samples and for sensitizing NMR detection, spectral broadening in frozen protein samples is a common experimental challenge. One hypothesis explaining the additional linewidth is that a variety of conformations are in rapid equilibrium at room temperature and become frozen, creating an inhomogeneous distribution at cryogenic temperatures. Here, we investigate conformational heterogeneity by measuring the backbone torsion angle (Ψ) in Escherichia coli Dihydrofolate Reductase (DHFR) at 105 K. Motivated by the particularly broad N chemical shift distribution in this and other examples, we modified an established NCCN Ψ experiment to correlate the chemical shift of Ni+1 to Ψi. With selective 15N and 13C enrichment of Ile, only the unique I60-I61 pair was expected to be detected in 13C'-15N correlation spectrum. For this unique amide, we detected three different conformation basins based on dispersed chemical shifts. Backbone torsion angles Ψ were determined for each basin: 114 ± 7° for the major peak and 150 ± 8° and 164 ± 16° for the minor peaks as contrasted with 118° for the X-ray crystal structure (and 118° to 130° for various previously reported structures). These studies support the hypothesis that inhomogeneous distributions of protein backbone torsion angles contribute to the lineshape broadening in low-temperature NMR spectra.
Assuntos
Temperatura Baixa , Proteínas , Temperatura , Espectroscopia de Ressonância Magnética , Conformação Proteica , Proteínas/química , Ressonância Magnética Nuclear BiomolecularRESUMO
Clinically, circle of Willis (CoW) is prone to anomaly and is also the predominant incidence site of intracranial aneurysms (IAs). This study aims to investigate the hemodynamic characteristics of CoW anomaly, and ascertain the mechanism of IAs initiation from the perspective of hemodynamics. Thus, the flow of IAs and pre-IAs were analyzed for one type of cerebral artery anomaly, that is, anterior cerebral artery A1 segment (ACA-A1) unilateral absence. Three patient geometrical models with IAs were selected from Emory University Open Source Data Center. IAs were virtually removed from the geometrical models to simulate the pre-IAs geometry. For calculation methods, a one-dimensional (1-D) solver and a three-dimensional (3-D) solver were combined to obtain the hemodynamic characteristics. The numerical simulation revealed that the average flow of Anterior Communicating Artery (ACoA) is almost zero when CoW is complete. In contrast, ACoA flow increases significantly in the case of ACA-A1 unilateral absence. For per-IAs geometry, the jet flow is found at the bifurcation between contralateral ACA-A1 and ACoA, which exhibits characteristics of high Wall Shear Stress (WSS) and high wall pressure in the impact region. It triggers the initiation of IAs from the perspective of hemodynamics. The vascular anomaly that leads to jet flow should be considered as a risk factor for IAs initiation.
Assuntos
Círculo Arterial do Cérebro , Aneurisma Intracraniano , Humanos , Adulto , Criança , Hemodinâmica , Fatores de Risco , Estresse MecânicoRESUMO
BACKGROUND: Ferroptosis, a newly form of regulated cell death (RCD), is characterized by iron dyshomeostasis and unrestricted lipid peroxidation. Emerging evidence depicts a pivotal role for ferroptosis in driving some pathological processes, especially in cancer. Triggering ferroptosis can suppress tumor growth and induce an anti-tumor immune response, denoting the therapeutic promises for targeting ferroptosis in the management of cancer. As an autophagic phenomenon, ferritinophagy is critical to induce ferroptosis by degradation of ferritin to release intracellular free iron. Recently, a great deal of effort has gone into designing and developing anti-cancer strategies based on targeting ferritinophagy to induce ferroptosis. CONCLUSION: This review delineates the regulatory mechanism of ferritinophagy firstly and summarizes the role of ferritinophagy-induced ferroptosis in cancer. Moreover, the strategies targeting ferritinophagy to induce ferroptosis are highlighted to unveil the therapeutic value of ferritinophagy as a target to manage cancer. Finally, the future research directions on how to cope with the challenges in developing ferritinophagy promoters into clinical therapeutics are discussed.
Assuntos
Ferroptose , Neoplasias , Humanos , Ferro/metabolismo , Ferro/farmacologia , Ferro/uso terapêutico , Ferritinas/metabolismo , Ferritinas/uso terapêutico , Neoplasias/metabolismo , AutofagiaRESUMO
OBJECTIVE: Multiple intracranial aneurysms (MIA) are prevalent. This study conducted hemodynamic calculations on MIA to analyze the effects of occlusion of the internal carotid artery (ICA) and middle cerebral artery (MCA) aneurysms on the hemodynamics of other arteries, as well as the issue of the treatment order for these aneurysms. METHODS: The models of 9 patients with MIA were selected for the study. A computational fluid dynamics model combining 1-dimension and 3-dimension was used to obtain the vascular flow pattern and wall pressure. RESULTS: There was increased pressure at the MCA and anterior cerebral artery (ACA) after occlusion of the aneurysm at the ICA. However, the pressure at the ICA has hardly changed after the aneurysm occlusion at the MCA. Occlusion of the aneurysm of different sizes at the MCA had almost no impact on the pressure at the ICA and ACA. For small aneurysm, the pressure of the ACA and MCA increases with decreasing size of the aneurysm at the ICA. After occlusion of a large aneurysm at the ICA, the impact on the pressure of the ACA and MCA is almost the same as after occlusion of a medium-sized aneurysm. CONCLUSIONS: If the treatment order of ICA and MCA aneurysms cannot be determined based on patient factors and aneurysm characteristics, the MCA aneurysm should be treated as a priority.
Assuntos
Aneurisma Intracraniano , Humanos , Hidrodinâmica , Artéria Cerebral Anterior , Hemodinâmica , Artéria Carótida InternaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Pyrrosia petiolosa (Christ) Ching (YBSW) is a Traditional Chinese medicine rich in chlorogenic acids. It is an important component in many Traditional Chinese medicinal hypoglycemic formulas and is commonly used by the Miao people to treat diabetes with good efficacy. Our previous research has suggested that chlorogenic acids may be the active ingredients in YBSW. AIM OF THE STUDY: To explore the mechanisms underlying the anti-type 2 diabetes mellitus (T2DM) hypoglycemic effects of chlorogenic acids contained in YBSW. MATERIALS AND METHODS: In vivo experiments, hematoxylin-eosin staining (HE) staining, and immunohistochemistry (IHC) were used to determine the effects of chlorogenic acids contained in YBSW in rats. mRNA expression profiling, microarray analysis, and network pharmacology were used to analyze the underlying mechanisms of the effects. Finally, apoptosis and changes in the related pathways were evaluated in vitro using a 3-(4,5-dimethyl-2-thia-zolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, quantitative real-time polymerase chain reaction, immunofluorescence (IF) assessment, and flow cytometry. RESULTS: After the administration of isochlorogenic acid B, the levels of triglycerides, serum total cholesterol, and fasting blood glucose significantly decreased. HE and IHC staining revealed that isochlorogenic acid B significantly increased insulin expression in islet cells. Using network pharmacology and RNA-seq Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, we screened the advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway. We also verified that YBSW and its chlorogenic acid can inhibit apoptosis and downregulate the expression of related mRNA in the AGE-RAGE pathway in RIN-m5f cells. CONCLUSIONS: YBSW exhibits a significant hypoglycemic effect, with chlorogenic acid being an effective component. The therapeutic effect of chlorogenic acids contained in YBSW is mainly realized by promoting insulin secretion and pancreatic tissue repair. Moreover, YBSW substantially mitigates apoptosis via the AGE-RAGE pathway in T2DM.
Assuntos
Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Animais , Ratos , Ácido Clorogênico/farmacologia , Ácido Clorogênico/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Perfilação da Expressão Gênica , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Simulação de Acoplamento Molecular , Farmacologia em Rede , RNA MensageiroRESUMO
BACKGROUND: Entecavir (ETV) is a potent and safe antiviral agent for patients with chronic hepatitis B (CHB); however, some patients may exhibit suboptimal response or resistance to ETV. Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil fumarate. AIM: To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to ETV. METHODS: A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia [Hepatitis B virus (HBV) DNA ≥ 20 IU/mL] or partial virologic response (HBV DNA < 20 IU/mL, but detectable) were enrolled in the study. The patients were randomly assigned to either continue ETV (0.5 mg) daily or switch to TAF (25 mg) daily for 48 wk. The primary endpoint was the proportion of patients who achieved a virologic response (HBV DNA level < 20 IU/mL) at week 48. Secondary endpoints included changes in serum alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and anti-HBe levels, and renal and bone safety parameters. RESULTS: At week 48, the proportion of patients who achieved a virologic response was significantly higher in the TAF group than in the ETV group (93.3% vs 66.7%, P = 0.012). The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group (-3.8 vs -2.4 Log10 IU/mL, P < 0.001). The rates of ALT normalization, HBeAg loss, HBeAg seroconversion, and HBsAg loss were not found to significantly differ between the two groups. None of the patients developed genotypic resistance to ETV or TAF. Both drugs were well tolerated, with no serious adverse events or discontinuations caused by adverse events. No significant changes were observed in the estimated glomerular filtration rate, serum creatinine level, or urine protein-to-creatinine ratio in either group. The TAF group had a significantly lower decrease in bone mineral density at the lumbar spine and hip than the ETV group (-0.8% vs -2.1%, P = 0.004; -0.6% vs -1.8%, P = 0.007, respectively). CONCLUSION: Switching from ETV to TAF is effective and safe for patients with CHB exhibiting a suboptimal response to ETV and may prevent further viral resistance and reduce renal and bone toxicity.
RESUMO
Breast cancer (BC) remains the foremost cause of cancer mortality globally, with neutrophils playing a critical role in its pathogenesis. As an essential tumor microenvironment (TME) component, neutrophils are emerging as pivotal factors in BC progression. Growing evidence has proved that neutrophils play a Janus- role in BC by polarizing into the anti-tumor (N1) or pro-tumor (N2) phenotype. Clinical trials are evaluating neutrophil-targeted therapies, including Reparixin (NCT02370238) and Tigatuzumab (NCT01307891); however, their clinical efficacy remains suboptimal. This review summarizes the evidence regarding the close relationship between neutrophils and BC, emphasizing the critical roles of neutrophils in regulating metabolic and immune pathways. Additionally, we summarize the existing therapeutic approaches that target neutrophils, highlighting the challenges, and affirming the rationale for continuing to explore neutrophils as a viable therapeutic target in BC management.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/metabolismo , Neutrófilos/metabolismo , Resultado do Tratamento , Microambiente Tumoral , Ensaios Clínicos como AssuntoRESUMO
Epstein-Barr virus (EBV), a double-stranded DNA virus belonging to the family Herpesviridae, infects more than 95% of healthy adults by attacking the host immune system. Here, a novel detection protocol, utilizing the modified multiple cross displacement amplification (MCDA) technique combined with a gold nanoparticles-based lateral flow biosensors (AuNPs-LFB), was devised and developed to detect EBV infection (termed EBV-MCDA-LFB assay). Ten MCDA primers targeting the EBNA-LP gene were designed, including CP1* primers modified with 6-carboxyfluorescein (FAM) and D1* primers modified with biotin. Then, nucleic acid templates extracted from various pathogens and whole blood samples were used to optimize and evaluate the EBV-MCDA-LFB assay. As a result, the lowest concentration of EBNA-plasmids, which can be detected by MCDA-LFB assay with an optimal reaction condition of 67°C for 30 min, was 10 copies/reaction. Here, the MCDA-LFB assay can detect all EBV pathogens used in the study, and no cross-reactions with non-EBV organisms were observed. Meanwhile, the entire detection workflow of the EBV-MCDA-LFB assay for whole blood samples, including DNA template preparation (25 min), EBV-MCDA amplification (30 min), and AuNPs-LFB-mediated validation (2-5 min), can be completed within 1 h. Taken together, the EBV-MCDA-LFB assay established in the current study is a rapid, simplified, sensitive, specific, and easy-to-obtain technique that can be used as a screening or diagnostic tool for EBV infection in clinical applications, especially in resource-poor regions.
RESUMO
BACKGROUND: The correlation between plasma adipose factor levels and Alzheimer's patients is not entirely clear. OBJECTIVE: We aimed to investigate associations between AD and plasma levels of three adipokines including plasma adiponectin, leptin, and resistin. METHODS: A single-center, cross-sectional study recruited AD patients (nâ=â148) and cognitively normal (CN) controls (nâ=â110). The multivariate logistic regression analysis was applied to determine associations of adiponectin, leptin, and resistin with the presence of AD. The receiver operating characteristic (ROC) analysis was employed to determine the diagnostic power of adiponectin, leptin and resistin for AD. RESULTS: After adjusted for the conventional risk factors, plasma levels of leptin (ORâ=â0.417, 95% CI: 0.272-0.638, pâ<â0.0001) and adiponectin (ORâ=â1.249, 95% CI: 1.151-1.354, pâ<â0.0001) were associated with the presence of AD. In total participants, the plasma adiponectin level was negatively correlated with MMSE scores (pâ<â0.0001) and was positively with CDR scores (pâ<â0.0001) and age (pâ<â0.0001). The plasma level of leptin was negatively correlated with CDR scores (pâ<â0.0001) and positively correlated with MMSE scores (pâ<â0.0001). Both adiponectin (pâ<â0. 0001) and leptin (pâ<â0. 0001) featured higher AUC than the random chance. CONCLUSIONS: Plasma adiponectin and leptin were associated with the presence, symptomatic severity, and diagnostic power of AD, suggesting a potential role of adipokines in the pathogenesis of AD.