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1.
Heliyon ; 10(9): e29955, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38726195

RESUMO

Purpose: The study investigates the value of the BRAFV600E mutation in determining the aggressiveness of papillary thyroid cancer (PTC) and its correlation with ultrasound features. Methods: The study selected 176 patients with BRAFV600E mutation and 80 without the mutation who underwent surgery at Guangxi Medical University Cancer Hospital. Clinical and pathological data were collected, focusing on BRAFV600E mutations and associated ultrasonic features. Correlation analysis, as well as univariate and multivariate logistic regression analysis, were conducted to identify independent risk factors for BRAFV600E mutation. The results were verified using a nomogram model. Results: The analysis results indicate that the BRAFV600E mutation correlates with tumor size, nodule size, taller-than-wide shape, margin, and shape of papillary thyroid cancer. The receiver operating characteristic curve was used to analyze the diagnostic effect of these features on BRAFV600E mutation. The results showed that nodule size had the most significant area under the curve (AUC = 0.665). Univariate and multivariate logistic regression analyses revealed that taller-than-wide shape ≥1, ill-defined margin, irregular shape, nodule size (≤1.40 cm), TT4 (>98.67 nmol/L), and FT3 (<4.14 pmol/L) were independent risk factors for BRAFV600E mutation. While considering all these factors in the nomogram, the Concordance index (C-index) remained high at 0.764. This suggests that the model has a good predictive effect. Conclusion: Ultrasound features including nodule size, taller-than-wide shape ≥1, ill-defined margins, irregular shape, higher TT4 levels, and lower FT3 levels were associated with papillary thyroid cancer aggressiveness and BRAFV600E mutation.

2.
J Virol ; 98(5): e0035024, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38591900

RESUMO

Feline calicivirus (FCV) is one of the few members of the Caliciviridae family that grows well in cell lines and, therefore, serves as a surrogate to study the biology of other viruses in the family. Conley et al. (14) demonstrated that upon the receptor engagement to the capsid, FCV VP2 forms a portal-like assembly, which might provide a channel for RNA release. However, the process of calicivirus RNA release is not yet fully understood. Our findings suggest that the separation of the FCV capsid from its genome RNA (gRNA) occurs rapidly in the early endosomes of infected cells. Using a liposome model decorated with the FCV cell receptor fJAM-A, we demonstrate that FCV releases its gRNA into the liposomes by penetrating membranes under low pH conditions. Furthermore, we found that VP2, which is rich in hydrophobic residues at its N-terminus, functions as the pore-forming protein. When we substituted the VP2 N-terminal hydrophobic residues, the gRNA release efficacy of the FCV mutants decreased. In conclusion, our results suggest that in the acidic environment of early endosomes, FCV VP2 functions as the pore-forming protein to mediate gRNA release into the cytoplasm of infected cells. This provides insight into the mechanism of calicivirus genome release.IMPORTANCEResearch on the biology and pathogenicity of certain caliciviruses, such as Norovirus and Sapovirus, is hindered by the lack of easy-to-use cell culture system. Feline calicivirus (FCV), which grows effectively in cell lines, is used as a substitute. At present, there is limited understanding of the genome release mechanism in caliciviruses. Our findings suggest that FCV uses VP2 to pierce the endosome membrane for genome release and provide new insights into the calicivirus gRNA release mechanism.


Assuntos
Calicivirus Felino , Proteínas do Capsídeo , Endossomos , Genoma Viral , RNA Viral , Calicivirus Felino/genética , Calicivirus Felino/metabolismo , Calicivirus Felino/fisiologia , Gatos , Endossomos/virologia , Endossomos/metabolismo , Animais , RNA Viral/metabolismo , RNA Viral/genética , Linhagem Celular , Proteínas do Capsídeo/metabolismo , Proteínas do Capsídeo/genética , Infecções por Caliciviridae/virologia , Infecções por Caliciviridae/metabolismo , Liberação de Vírus , Capsídeo/metabolismo , Lipossomos/metabolismo
3.
J Evid Based Med ; 17(1): 207-223, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38530771

RESUMO

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.


Assuntos
Gastroenteropatias , Medicina Integrativa , Humanos , Medicina Tradicional Chinesa , Gastroenteropatias/prevenção & controle , Medicina Baseada em Evidências
4.
Dentomaxillofac Radiol ; 53(1): 60-66, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38214943

RESUMO

OBJECTIVES: This study aims to evaluate the morphological features of gubernacular tract (GT) for erupting permanent mandibular canines at different ages from 5 to 9 years old with a three-dimensional (3D) measurement method. METHODS: The cone-beam CT images of 50 patients were divided into five age groups. The 3D models of the GT for mandibular canines were reconstructed and analysed. The characteristics of the GT, including length, diameter, ellipticity, tortuosity, superficial area, volume, and the angle between the canine and GT, were evaluated using a centreline fitting algorithm. RESULTS: Among the 100 GTs that were examined, the length of the GT for mandibular canines decreased between the ages of 5 and 9 years, while the diameter increased until the age of 7 years. Additionally, the ellipticity and tortuosity of the GT decreased as age advanced. The superficial area and volume exhibited a trend of initially increasing and then decreasing. The morphological variations of the GT displayed heterogeneous changes during different periods. CONCLUSIONS: The 3D measurement method effectively portrayed the morphological attributes of the GT for mandibular canines. The morphological characteristics of the GT during the eruption process exhibited significant variations. The variations in morphological changes may indicate different stages of mandibular canine eruption.


Assuntos
Maxila , Erupção Dentária , Humanos , Pré-Escolar , Criança , Tomografia Computadorizada de Feixe Cônico/métodos , Dente Canino/diagnóstico por imagem
5.
Artigo em Inglês | MEDLINE | ID: mdl-38206597

RESUMO

ABSTRACT: The purpose of this study was to provide an evidence map for explaining research trends and gaps. Four databases and CPGs-related websites were searched up to March 2022. Basic information, methodological quality, reporting quality of CPGs, and similar stroke recommendations were extracted. The methodological and reporting quality of stroke CPGs were evaluated using the AGREE II instrument and the RIGHT checklist. The bubble plot format of the evidence map helped visualize the overall quality. Data management and analysis were performed using Excel 2013 and SPSS 22.0 software. A total of 12 CPGs, published between 1997 and 2020 were included for in-depth analysis. The identified CPGs had a mixed quality and scored poorly in the developmental rigor and applicability domains by AGREE II. According to the RIGHT checklist, field four (clarity of expression) showed the highest (79.2%), and field three (rigor of formulation) secured the lowest (28%) reporting rates. The stroke rehabilitation recommendations primarily focused on organizational management, timing and intensity, rehabilitation and nutritional management of dysphagia, return to work, communication, speech, and language function. This would promote improvement in developing trustworthy CPGs for stroke rehabilitation.

6.
J Biol Chem ; 300(1): 105539, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38072054

RESUMO

L-ergothioneine is widely distributed among various microbes to regulate their physiology and pathogenicity within complex environments. One of the key steps in the ergothioneine-biosynthesis pathway, the C-S bond cleavage reaction, uses the pyridoxal 5'-phosphate dependent C-S lyase to produce the final product L-ergothioneine. Here, we present the crystallographic structure of the ergothioneine-biosynthesis C-S lyase EgtE from Mycobacterium smegmatis (MsEgtE) represents the first published structure of ergothioneine-biosynthesis C-S lyases in bacteria and shows the effects of active site residues on the enzymatic reaction. The MsEgtE and the previously reported ergothioneine-biosynthesis C-S lyase Egt2 from Neurospora crassa (NcEgt2) fold similarly. However, discrepancies arise in terms of substrate recognition, as observed through sequence and structure comparison of MsEgtE and NcEgt2. The structural-based sequence alignment of the ergothioneine-biosynthesis C-S lyase from fungi and bacteria shows clear distinctions among the recognized substrate residues, but Arg348 is critical and an extremely conserved residue for substrate recognition. The α14 helix is exclusively found in the bacteria EgtE, which represent the most significant difference between bacteria EgtE and fungi Egt2, possibly resulting from the convergent evolution of bacteria and fungi.


Assuntos
Ergotioneína , Liases , Mycobacterium , Ergotioneína/química , Ergotioneína/metabolismo , Fungos/metabolismo , Liases/química , Liases/metabolismo , Mycobacterium/metabolismo , Mycobacterium smegmatis/química , Mycobacterium smegmatis/enzimologia , Modelos Moleculares , Estrutura Quaternária de Proteína , Estrutura Terciária de Proteína
7.
Biol Trace Elem Res ; 202(3): 850-865, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37291467

RESUMO

The effects of metal exposure on kidney function have been reported in previous literature. There is limited and inconsistent information on the associations between individual and combined exposures to metals and kidney function among the middle-aged and older population. The aim of this study was to clarify the associations of exposure to individual metals with kidney function while accounting for potential coexposure to metal mixtures and to evaluate the joint and interactive associations of blood metals with kidney function. A total of 1669 adults aged 40 years and older were enrolled in the present cross-sectional study using the 2015-2016 National Health and Nutrition Examination Survey (NHANES). Single-metal and multimetal multivariable logistic regression models, quantile G-computation, and Bayesian kernel machine regression models (BKMR) were fitted to explore the individual and joint associations of whole blood metals [lead (Pb), cadmium (Cd), mercury (Hg), cobalt (Co), manganese (Mn), and selenium (Se)] with the odds of decreased estimated glomerular filtration rate (eGFR) and albuminuria. A decreased eGFR was defined as an eGFR ≤ 60 mL/min per 1.73 m2, and albuminuria was categorized as a urinary albumin-creatinine ratio (UACR) of ≥ 30.0 mg/g. The results from quantile G-computation and BKMR indicated positive associations between exposure to the metal mixture and the prevalence of decreased eGFR and albuminuria (all P values < 0.05). These positive associations were mainly driven by blood Co, Cd, and Pb. Furthermore, blood Mn was identified as an influential element contributing to an inverse correlation with kidney dysfunction within metal mixtures. Increasing blood Se levels were negatively associated with the prevalence of decreased eGFR and positively associated with albuminuria. In addition, a potential pairwise interaction between Mn-Co on decreased eGFR was identified by BKMR analysis. Findings from our study suggested a positive association between exposure to the whole blood metal mixture and decreased kidney function, with blood Co, Pb, and Cd being the main contributors to this association, while Mn demonstrated an inverse relationship with renal dysfunction. However, as our study was cross-sectional in nature, further prospective studies are warranted to better understand the individual and combined effects of metals on kidney function.


Assuntos
Mercúrio , Metais Pesados , Selênio , Adulto , Pessoa de Meia-Idade , Humanos , Idoso , Cádmio , Inquéritos Nutricionais , Estudos Transversais , Albuminúria , Teorema de Bayes , Chumbo , Manganês , Cobalto , Rim , Metais Pesados/efeitos adversos
8.
JMIR Serious Games ; 11: e43181, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38062643

RESUMO

Background: In the context of training specialist nurses and nursing education, a game-based mobile app was used as a simulation to teach intensive critical care specialist nurses the knowledge and skills of extracorporeal membrane oxygenation (ECMO) pipeline preflushing. Objective: This study aimed to evaluate the impact of a game-based mobile app on improving ECMO pipeline preflushing skills in intensive critical care specialist nurses. Methods: A total of 86 intensive critical care specialist nurses who were learning ECMO for the first time were included in this study. The nurses were divided into 2 groups: a control group (n=43) and an experimental group (n=43). Participants in the experimental group used a game-based mobile app for simulation exercises; the control group received no additional intervention. All participants took a theoretical test and a skill operation test at the beginning of the study and 1 week later. The differences in scores between the 2 groups were compared, and the learning curve of the experimental group was observed. Results: The final theoretical test scores (88.44 and 85.02) and skill operation test scores (89.42 and 86.33) of the experimental group and control group, respectively, were significantly higher than those of the initial tests (theoretical test scores: 75.88 and 74.42; skill operation test scores: 75.44 and 75.93; all P<.001). The scores of the final theoretical test (88.44) and the final skill operation test (89.42) in the experimental group were higher than the scores of the control group (85.02; P<.001 and 86.33; P<.001, respectively). Learning curve analysis showed that the experimental group needed an average of 17 operations to master the skill. Conclusions: This study suggests that a game-based mobile app may be more effective for intensive critical care specialist nurses in ECMO pipeline preflushing education than traditional Chinese lecture-practice education.

9.
Nanoscale Adv ; 5(22): 6017-6037, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37941954

RESUMO

Wound healing is a dynamic and complex process in which the microenvironment at the wound site plays an important role. As a common material for wound healing, dressings accelerate wound healing and prevent external wound infections. Hydrogels have become a hot topic in wound-dressing research because of their high water content, good biocompatibility, and adjustable physical and chemical properties. Intelligent hydrogel dressings have attracted considerable attention because of their excellent environmental responsiveness. As smart polymer hydrogels, thermosensitive hydrogels can respond to small temperature changes in the environment, and their special properties make them superior to other hydrogels. This review mainly focuses on the research progress in thermosensitive intelligent hydrogel dressings for wound healing. Polymers suitable for hydrogel formation and the appropriate molecular design of the hydrogel network to achieve thermosensitive hydrogel properties are discussed, followed by the application of thermosensitive hydrogels as wound dressings. We also discuss the future perspectives of thermosensitive hydrogels as wound dressings and provide systematic theoretical support for wound healing.

11.
Int J Mol Sci ; 24(22)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38003450

RESUMO

Fibrosis commonly arises from salivary gland injuries induced by factors such as inflammation, ductal obstruction, radiation, aging, and autoimmunity, leading to glandular atrophy and functional impairment. However, effective treatments for these injuries remain elusive. Transforming growth factor-beta 1 (TGF-ß1) is fundamental in fibrosis, advancing fibroblast differentiation into myofibroblasts and enhancing the extracellular matrix in the salivary gland. The involvement of the SMAD pathway and reactive oxygen species (ROS) in this context has been postulated. Metformin, a type 2 diabetes mellitus (T2DM) medication, has been noted for its potent anti-fibrotic effects. Through human samples, primary salivary gland fibroblasts, and a rat model, this study explored metformin's anti-fibrotic properties. Elevated levels of TGF-ß1 (p < 0.01) and alpha-smooth muscle actin (α-SMA) (p < 0.01) were observed in human sialadenitis samples. The analysis showed that metformin attenuates TGF-ß1-induced fibrosis by inhibiting SMAD phosphorylation (p < 0.01) through adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-independent pathways and activating the AMPK pathway, consequently suppressing NADPH oxidase 4 (NOX4) (p < 0.01), a main ROS producer. Moreover, in rats, metformin not only reduced glandular fibrosis post-ductal ligation but also protected acinar cells from ligation-induced injuries, thereby normalizing the levels of aquaporin 5 (AQP5) (p < 0.05). Overall, this study underscores the potential of metformin as a promising therapeutic option for salivary gland fibrosis.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Ratos , Humanos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Metformina/farmacologia , Metformina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fibrose , Fibroblastos/metabolismo , Glândulas Salivares/metabolismo
12.
BMJ Open ; 13(10): e074128, 2023 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-37816556

RESUMO

INTRODUCTION: The COVID-19 pandemic posed a detrimental impact on the conduct of non-COVID-19 related clinical trials, raising concerns about the completeness of these studies and waste of resources. While several measures and strategies have been suggested to address these issues, a thorough and timely summarisation is still lacking. Therefore, our aim is to conduct a scoping review to summarise the negative effects of COVID-19 on non-COVID-19 clinical trials, outline the effective measures for mitigating these impacts, and provide insights for future pandemics. METHODS AND ANALYSIS: This scoping review will be conducted in line with the Joanna Briggs Institute's scoping review methodological framework, and the results will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Relevant articles will be searched in PubMed, Embase and the Cochrane Library from 1 December 2019 to 1 July 2023. We will also screen the reference lists of the included studies manually to identify more potentially relevant articles. Articles focusing on the adverse impacts of COVID-19 on non-COVID-19 clinical trials and effective measures for mitigating them will be included. Two investigators will perform study selection and data extraction independently. A narrative summary as well as a descriptive analysis of the basic characteristics and key results of the included studies will be performed. ETHICS AND DISSEMINATION: Ethical approval is not required, as this scoping review will be completed based only on published literature. The findings of this scoping review will be disseminated through a peer-reviewed publication and/or conference presentations.


Assuntos
COVID-19 , Humanos , Pandemias , Narração , Revisão por Pares , PubMed , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Literatura de Revisão como Assunto
13.
Fish Shellfish Immunol ; 143: 109182, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37879511

RESUMO

As an essential micronutrient, copper is crucial in aquatic organisms' growth and development. Numerous studies have consistently reported that excessive intake of copper can have harmful effects on organisms. However, there are limited studies on the impact of copper on the intestine of the swamp eel (Monopterus albus). This study aimed to investigate the changes of intestinal histopathology, tight junction complex, immune response, and microbiota in swamp eel treated with 0 mg/L Cu2+, 0.05 mg/L Cu2+, and 0.10 mg/L Cu2+ for 56 d. Intestinal histopathology showed major changes such as the increased number of erythrocytes and goblet cells in the lamina propria, and separation of the lamina propria. The expression of genes involved in tight junction complex (ZO-1, Claudin-3, Claudin-12 and Claudin-15) was significantly changed. In addition, copper exposure significantly increased the mRNA levels of TLR3, TLR7, TLR8, NF-κB, I-κB, TNF-α and IL-8, especially in 0.10 mg/L Cu2+ group. In contrast, the relative expression level of anti-inflammatory cytokine TGF-ß was significantly decreased after exposure to copper. Analysis of the intestinal microbiome showed the intestinal microbiota of swamp eels in the control and copper exposure groups were dominated by Firmicutes and Proteobacteria at the phylum level. Notably, copper exposure changed the diversity of the intestinal microbiota and decreased the relative abundance of Firmicutes and Proteobacteria in the intestine of swamp eel. Collectively, this study demonstrates that chronic copper exposure induces intestinal pathologic changes and inflammatory response, disrupts the intestinal microbial diversity and microbiota composition, and decreases intestinal barrier function in swamp eel, which enhances our understanding of copper-induced intestinal toxicity in fish.


Assuntos
Microbioma Gastrointestinal , Smegmamorpha , Animais , Cobre/toxicidade , Cobre/metabolismo , Junções Íntimas , Intestinos , Imunidade
14.
Campbell Syst Rev ; 19(4): e1354, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37771463

RESUMO

This is the protocol for an evidence and gap map. The objectives are as follows: To map available randomized control trials, economic evaluations, and systematic reviews that assess the effectiveness and cost-effectiveness of non-pharmacological interventions for older people with a diagnosis of depression and identify any existing gaps in the evidence that can inform future research.

15.
Medicine (Baltimore) ; 102(39): e35348, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37773863

RESUMO

The combination of mRNA and lncRNA profiles for establishing an integrated mRNA-lncRNA prognostic signature has remained unexplored in cholangiocarcinoma (CCA) patients. We utilized a training dataset of 36 samples from The Cancer Genome Atlas dataset and a validation cohort (GSE107943) of 30 samples from Gene Expression Omnibus. Two mRNAs (CFHR3 and PIWIL4) and 2 lncRNAs (AC007285.1 and AC134682.1) were identified to construct the integrated signature through a univariate Cox regression (P-value = 1.35E-02) and a multivariable Cox analysis (P-value = 3.07E-02). Kaplan-Meier curve showed that patients with low risk scores had notably prolonged overall survival than those with high risk scores (P-value = 4.61E-03). Subsequently, the signature was validated in GSE107943 cohort with an area under the curve of 0.750 at 1-year and 0.729 at 3-year. The signature was not only independent from diverse clinical features (P-value = 3.07E-02), but also surpassed other clinical characteristics as prognostic biomarkers with area under the curve of 0.781 at 3-year. Moreover, the weighted gene co-expression network analysis and gene enrichment analyses found that the integrated signature were associated with metabolic-related biological process and lipid metabolism pathway, which has been implicated in the pathogenesis of CCA. Taken together, we developed an integrated mRNA-lncRNA signature that had an independent prognostic value in the risk stratification of patients with CCA.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Colangiocarcinoma/genética , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos
16.
J Clin Epidemiol ; 162: 160-168, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37659583

RESUMO

OBJECTIVES: Randomized controlled trials are the gold-standard for determining therapeutic efficacy, but are often unrepresentative of real-world settings. Statistical transportation methods (hereafter transportation) can partially account for these differences, improving trial applicability without breaking randomization. We transported treatment effects from two heart failure (HF) trials to a HF registry. STUDY DESIGN AND SETTING: Individual-patient-level data from two trials (Carvedilol or Metoprolol European Trial (COMET), comparing carvedilol and metoprolol, and digitalis investigation group trial (DIG), comparing digoxin and placebo) and a Scottish HF registry were obtained. The primary end point for both trials was all-cause mortality; composite outcomes were all-cause mortality or hospitalization for COMET and HF-related death or hospitalization for DIG. We performed transportation using regression-based and inverse odds of sampling weights (IOSW) approaches. RESULTS: Registry patients were older, had poorer renal function and received higher-doses of loop-diuretics than trial participants. For each trial, point estimates were similar for the original and IOSW (e.g., DIG composite outcome: OR 0.75 (0.69, 0.82) vs. 0.73 (0.64, 0.83)). Treatment effect estimates were also similar when examining high-risk (0.64 (0.46, 0.89)) and low-risk registry patients (0.73 (0.61, 0.86)). Similar results were obtained using regression-based transportation. CONCLUSION: Regression-based or IOSW approaches can be used to transport trial effect estimates to patients administrative/registry data, with only moderate reductions in precision.


Assuntos
Insuficiência Cardíaca , Metoprolol , Humanos , Carvedilol/uso terapêutico , Digoxina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização , Metoprolol/uso terapêutico , Resultado do Tratamento
17.
Transl Cancer Res ; 12(8): 2033-2047, 2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37701104

RESUMO

Background: N6-methyladenosine (m6A) has a critical role in the development and progression of cancer. However, the genetic and epigenetic patterns, as well as tumor microenvironment (TME) infiltration characteristics of m6A regulators in colorectal cancer (CRC) remain largely unknown. Methods: Molecular patterns of m6A modifications of 24 m6A regulators in CRC samples were evaluated using data from The Cancer Genome Atlas (TCGA). Mutations, copy number variations (CNVs), DNA methylation, and chromatin accessibility were examined to investigate the underlying mechanisms of the aberrant expression of m6A regulators. Correlations between m6A-related genes and TME cell-infiltrating characteristics were evaluated using Tumor Immune Estimation Resource (TIMER). Results: The m6A regulators were frequently dysregulated in CRC, with two downregulated and 16 upregulated. All the m6A regulators had mutations (frequency ranging from 0.9% to 7%), with active mutations tending to occur in RBM15 and inactive mutations in ZC3H13. Only five m6A regulators had CNV frequency greater than 1%: YTHDC2 (2.4%), YTHDF1 (7.0%), YTHDF3 (1.9%), VIRMA (1.7%), and ZC3H13 (3.0%). The copy numbers of these five genes were positively correlated with their expression levels. The m6A regulators frequently showed imbalanced methylation in CRC, with hypomethylation of YTHDF2, IGF2BP3, FTO, and hypermethylation of HNRNPC, METTL3, and WTAP. Most m6A regulators had high chromatin accessibility, which was positively correlated with their gene expression. IGF2BP1 was identified as an independent prognostic factor for overall survival. Moreover, the expression of most m6A regulators was positively correlated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Conclusions: Aberrant expression of m6A regulators is associated with mutation, CNV, and chromatin accessibility, owing to both genetic and epigenetic modifications. The TME infiltration characterization of m6A regulators could guide the development of more effective immunotherapy strategies in CRC.

18.
Artigo em Inglês | MEDLINE | ID: mdl-37661043

RESUMO

Due to its water solubility and wide applicability, enrofloxacin hydrochloride (EH) may enter aquatic ecosystems and cause negative effects on aquatic organisms. This study aimed to explore toxicological effects via serological changes and neurotoxicity, which were induced by EH exposure in crucian carp (Carassius auratus var. Pengze). The drug residues in brain tissue and protein content in serum were determined to analyze serological changes. Alterations in brain tissue structure and function, cerebral microvessels permeability, and the expressions of gene and protein regarding blood-brain barrier (BBB) were studied to reflect the neurotoxicity. Employing a validated high-performance liquid chromatography (HPLC) method, EH residues could be detected at various time-points throughout the experiment. Enzyme-linked immunosorbent assay (ELISA) showed that EH increased the levels of S100B, NSE and GFAP proteins in serum. Additionally, there was a significant positive correlation between serum S100B, NSE protein contents and EH residues (P < 0.05). Hematoxylin and eosin (H&E) staining revealed brain damage from EH exposure by the formation of vacuoles in brain glial cells, pyknosis of the nucleus, and a decrease in cell population density. Transmission electron microscope (TEM) revealed morphological changes in microvessels and condensation of astrocyte nucleus. Evans blue (EB) permeability test visualized an obvious increase in cerebral microvessels leakage. The real-time quantitative PCR (qPCR) results indicated that EH up-regulated the mRNA expression levels of S100B, NSE and GFAP, down-regulated the mRNA expression levels of P-gp, ZO-1, Occludin and Claudin-5. The Western blot (WB) results demonstrated increased NSE and GFAP protein expressions, decreased P-gp and Occludin protein expressions following EH exposure in brain, in consistent with the gene expressions, respectively. In conclusion, these findings indicated that EH brought about marked rise in serum biomarker levels and disrupted the central nervous system (CNS) of crucian carp. These data would help elucidate the mechanism underlying EH-induced neurotoxicological effects.


Assuntos
Carpas , Síndromes Neurotóxicas , Animais , Enrofloxacina/toxicidade , Ecossistema , Ocludina , RNA Mensageiro
19.
Foods ; 12(16)2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37628127

RESUMO

In recent years, food safety caused by foodborne pathogens and spoilage bacteria has become a major public health problem worldwide. Bacteriocins are a kind of antibacterial peptide synthesized by microbial ribosomes, and are widely used as food preservatives. However, when used individually bacteriocins may have limitations such as high cost of isolation and purification, narrow inhibitory spectrum, easy degradation by enzymes, and vulnerability to complex food environments. Numerous studies have demonstrated that co-treatment with bacteriocins and a variety of chemical substances can have synergistic antibacterial effects on spoilage microorganisms and foodborne pathogens, effectively prolonging the shelf life of food and ensuring food safety. Therefore, this paper systematically summarizes the synergistic bacteriostatic strategies of bacteriocins in combination with chemical substances such as essential oils, plant extracts, and organic acids. The impacts of bacteriocins when used individually and in combination with other chemical substances on different food substrates are clarified, and bacteriocin-chemical substance compositions that enhance antibacterial effectiveness and reduce the potential negative effects of chemical preservatives are highlighted and discussed. Combined treatments involving bacteriocins and different kinds of chemical substances are expected to be a promising new antibacterial method and to become widely used in both the food industry and biological medicine.

20.
J Interv Med ; 6(2): 53-58, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37409058

RESUMO

With the widespread adoption of ultrasound guidance, Seldinger puncture techniques, and intracardiac electrical positioning technology for the placement of peripherally inserted central catheters in recent years, an increasing number of medical staff and patients now accept peripheral placement of totally implantable venous access devices (TIVADs) in the upper arm. This approach has the advantage of completely avoiding the risks of hemothorax, pneumothorax, and neck and chest scarring. Medical specialties presently engaged in this study in China include internal medicine, surgery, anesthesiology, and interventional departments. However, command over implantation techniques, treatment of complications, and proper use and maintenance of TIVAD remain uneven among different medical units. Moreover, currently, there are no established quality control standards for implantation techniques or specifications for handling complications. Thus, this expert consensus is proposed to improve the success rate of TIVAD implantation via the upper-arm approach, reduce complication rates, and ensure patient safety. This consensus elaborates on the technical indications and contraindications, procedures and technical points, treatment of complications, and the use and maintenance of upper-arm TIVAD, thus providing a practical reference for medical staff.

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