RESUMEN
BACKGROUND: The increasing problem of bacterial resistance, particularly with quinolone-resistant Escherichia coli (QnR eco) poses a serious global health issue. METHODS: We collected data on QnR eco resistance rates and detection frequencies from 2014 to 2021 via the China Antimicrobial Resistance Surveillance System, complemented by meteorological and socioeconomic data from the China Statistical Yearbook and the China Meteorological Data Service Centre (CMDC). Comprehensive nonparametric testing and multivariate regression models were used in the analysis. RESULT: Our analysis revealed significant regional differences in QnR eco resistance and detection rates across China. Along the Hu Huanyong Line, resistance rates varied markedly: 49.35 in the northwest, 54.40 on the line, and 52.30 in the southeast (P = 0.001). Detection rates also showed significant geographical variation, with notable differences between regions (P < 0.001). Climate types influenced these rates, with significant variability observed across different climates (P < 0.001). Our predictive model for resistance rates, integrating climate and healthcare factors, explained 64.1% of the variance (adjusted R-squared = 0.641). For detection rates, the model accounted for 19.2% of the variance, highlighting the impact of environmental and healthcare influences. CONCLUSION: The study found higher resistance rates in warmer, monsoon climates and areas with more public health facilities, but lower rates in cooler, mountainous, or continental climates with more rainfall. This highlights the strong impact of climate on antibiotic resistance. Meanwhile, the predictive model effectively forecasts these resistance rates using China's diverse climate data. This is crucial for public health strategies and helps policymakers and healthcare practitioners tailor their approaches to antibiotic resistance based on local environmental conditions. These insights emphasize the importance of considering regional climates in managing antibiotic resistance.
Asunto(s)
Proteínas de Escherichia coli , Quinolonas , Escherichia coli , China/epidemiología , Farmacorresistencia Bacteriana , Antibacterianos/farmacologíaRESUMEN
BACKGROUND: In recent years, the scale of personnel training for clinical pharmacy professionals in China has expanded increasingly, however, the shortage of clinical pharmacists is still prominent. In 2018, the Ministry of Education of China released national standards for the teaching quality of undergraduate majors at regular colleges and universities, which has developed a core policy for undergraduate clinical pharmacy training. To explore the training methods for clinical pharmacy professionals in China and to promote the healthy and sustainable development of the clinical pharmacy education system. This study comparatively analyzed the training programs for clinical pharmacy undergraduates in China's ten universities, discussed training programs suitable for clinical pharmacy professionals in China. METHODS: The clinical pharmacy education programs in these ten universities were obtained through official school websites or by interviewing relevant people, and then compared and analyzed. RESULTS: The school with the largest number of courses and the most class hours in general courses is University A1 (34 courses, 1316 class hours), and the school with the most credits is University B1 (75.5 credits). The schools with the largest number of courses and the most class hours in the basic courses are University A1 (50 courses, 1997 class hours), and the schools with the most credits are University B3 and University B1 (105.5 credits). The schools with the largest number of courses in the core courses are University C1 (23 courses), and the school with the most credits and class hours is University B2 (51 credits, 914 class hours). The school with the most class hours in practical teaching is University B6 (1406 class hours), and the schools with the longest internship time are University A1 and University B6 (52 weeks). CONCLUSIONS: There was substantial variation in programs. There remains a gap between the existing educational model and clinical training in pharmacy in China and developed countries. China should explore the most appropriate method for undergraduate education in clinical pharmacy based on studying foreign excellent educational models and the experience of China.
Asunto(s)
Educación en Farmacia , Farmacia , Humanos , Universidades , Curriculum , China , Estudiantes , Educación en Farmacia/métodosRESUMEN
Substantial improvement of rotation driving accuracy is urgently needed and facing challenges. Miniature bidirectional rotary actuators with high-precision and controllable fallback rate require novel driving principles. Here, on the basis of a proposed biomimetic stick-slip motion principle, a novel piezoelectric-thermal coupling bidirectional rotary actuator was developed. The integrated mantis grasping leglike biomimetic claws and heating rods could realize the clockwise macroscopic rotation and anticlockwise macroscopic fallback of a cylindrical rotator, generated by piezoelectric stick-slip and thermal expansion, respectively. The rotation fallback was effectively inhibited at relatively lower frequencies and higher voltages, as a slight fallback rate of 0.095 was confirmed in term of 0.5 Hz and 80 V. An extraordinary piezoelectric-driven macroscopic rotation resolution of 0.2 µrad and thermal-induced microscopic resolution of 0.00073°/°C were experimentally revealed with the aid of real-time observation of the clockwise slow sticking and anticlockwise instantaneous slipping processes by using three-dimensional optical imaging.
Asunto(s)
Biomimética , Movimiento (Física)RESUMEN
PURPOSE: To describe and analyze the clinical prognosis of infants diagnosed of familial exudative vitreoretinopathy (FEVR) with single gene mutation in long-term follow-up. METHODS: A retrospective case study was conducted on 355 FEVR infants with single positive gene. RESULT: Of the 335 single-gene positive infant FEVR cases (under 3 years old), 20% (n = 67) was diagnosed of strabismus at first visit. Staging of various genotypes was different (P < 0.001). Patients with NDP mutations presented the most severe clinical phenotypes and patients with ZNF408 mutations presented the mildest clinical phenotypes. Most infants underwent surgery under 1 year old (5th stage 75 of 108 [69.44%]). The axial length of different genotypes showed no significant difference (P = 0.2891). The 1st to 3rd stage cases were given intravitreal injection and/or retina photocoagulation with the last follow-up vision above 20/67. The 4th to 5th stage cases received the transcorneal vitrectomy with lensectomy or lens sparing vitrectomy (LSV), whose lens maintained transparent after LSV (11/14[78.58%]). After 2 to 10 years of follow-up, 37.96% (41/108) of post-surgery cases showed retinal funnel-like unfold and posterior pole unfold, 69.57% (16/ 23) of which received second surgery for closure of pupil with good prognosis. At the last follow-up, 20% (60/300) were with vision above 20/200. CONCLUSION: LRP5 gene mutation was the most common mutation in FEVR patients. The severity of the clinical phenotype varied with different gene mutations. The main surgical methods for cases at Stage 4-5 were transcorneal vitrectomy with lensectomy or LSV. The earlier FEVR occurred, the worse prognosis would be. Active surgical intervention and lens sparing were necessary for cases at Stage 4-5.
Asunto(s)
Enfermedades Hereditarias del Ojo , Enfermedades de la Retina , Proteínas de Unión al ADN/genética , Vitreorretinopatías Exudativas Familiares , Humanos , Mutación , Linaje , Pronóstico , Enfermedades de la Retina/diagnóstico , Estudios Retrospectivos , Factores de Transcripción/genéticaRESUMEN
Purpose: Retinoblastoma (RB) is a pediatric ocular malignancy due to biallelic inactivation of the RB1 gene. Genetic testing is critically important for treatment decisions for this disease. Targeted next-generation sequencing (NGS) has been demonstrated to be an effective strategy for discovering all types of mutations in the RB1 gene. The aim of this study is the application of targeted NGS in a cohort of Chinese patients with retinoblastoma to identify germline mutations in the RB1 gene. Methods: Blood samples were collected from 149 unrelated probands with retinoblastoma (62 bilaterally and 87 unilaterally) and their parent(s). Genomic DNA was analyzed with custom panel-based targeted NGS, and the panel was designed to include exons 1-27 of the RB1 gene with flanking intronic sequences. Single nucleotide variations (SNVs) and small insertions/deletions (InDels) identified were confirmed with Sanger sequencing. If the Sanger sequencing of a low-frequency variant (LFV) detected with targeted NGS was negative, PCR-based deep NGS was conducted for added confirmation. Copy number variations (CNVs) detected with targeted NGS were confirmed with multiplex ligation-dependent probe amplification (MLPA). Results: Overall, 74 germline mutations were detected in 48.3% of the probands (72/149, 56 bilateral and 16 unilateral cases). The total detection rate in the bilateral cases was 90.3% (56/62). These mutations included 64 SNVs and InDels (25 nonsense, 20 splicing, ten frameshift, eight missense, and one synonymous variants) and ten CNVs. All CNVs were confirmed with MLPA. Twenty-four (32.4%, 24/74) variants detected were novel, including nine splicing, six frameshift, five missense, and four nonsense variants. Eight LFVs (10.8%, 8/74) were found with targeted NGS; six of which were identified with Sanger sequencing, and two were identified with PCR-based deep NGS (13.16% and 3.000% mutant rates, respectively). Conclusions: This study expanded the spectrum of germline mutations in RB1 using targeted NGS technology, which is a cost-saving and efficient method for genetic sequencing of retinoblastoma and may improve the molecular diagnosis of retinoblastoma.
Asunto(s)
Pueblo Asiatico/genética , Mutación de Línea Germinal/genética , Neoplasias de la Retina/genética , Proteínas de Unión a Retinoblastoma/genética , Retinoblastoma/genética , Ubiquitina-Proteína Ligasas/genética , Empalme Alternativo/genética , Preescolar , China/epidemiología , Codón sin Sentido/genética , Variaciones en el Número de Copia de ADN/genética , Análisis Mutacional de ADN , Exones/genética , Femenino , Mutación del Sistema de Lectura/genética , Genes de Retinoblastoma/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Masculino , Mutación Missense/genética , Linaje , Reacción en Cadena de la PolimerasaRESUMEN
Purpose: Familial exudative vitreoretinopathy (FEVR) is an inherited retinal vascular disease genetically heterogeneous with multiple causative genes. The aim of this study is to report five novel copy number variation (CNV) regions in FEVR patients and to investigate the possible contributions of novel CNVs to FEVR. Methods: In this study, 824 FEVR families were collected. All cases were performed using the targeted next generation sequencing (NGS) assay, and families with no definite pathogenic mutations in FEVR genes were screened for CNVs according to the NGS results. Droplet digital polymerase chain reaction (ddPCR) testing was introduced to validate the screened CNV regions. We also reviewed the clinical presentations of the probands and affected family members associated with the novel CNVs and conducted segregation analysis. Results: Five CNVs in five patients were detected in this study: heterozygous deletions of kinesin family member 11 (KIF11) exons 2-4, KIF11 exon 11, KIF11 exons 1-10, tetraspanin-12 (TSPAN12) exons 1-3, and low-density lipoprotein receptor-related protein 5 (LRP5) exons 19-21. Among the five affected families, TSPAN12 exons 1-3 heterozygous deletion and LRP5 exons 19-21 heterozygous deletion originate from the mother and the father of the proband, respectively. No other family members manifested as FEVR except for the probands. The correlation between disease severity and CNV loci seems uncertain. Conclusions: Five novel CNV loci in FEVR patients were uncovered in this study, including one maternally-inherited and one paternally-inherited CNV region. Though there is no evidence of co-segregation between these CNVs and FEVR, our findings suggest novel genetic risk factors for FEVR.
Asunto(s)
Enfermedades Hereditarias del Ojo , Cinesinas/genética , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Enfermedades de la Retina , Tetraspaninas , Variaciones en el Número de Copia de ADN , Análisis Mutacional de ADN , Enfermedades Hereditarias del Ojo/genética , Vitreorretinopatías Exudativas Familiares , Humanos , Mutación , Linaje , Fenotipo , Enfermedades de la Retina/genética , Tetraspaninas/genéticaRESUMEN
Age-related macular degeneration is a progressive ocular disease that is the leading cause of vision loss among elderly. AMD usually is divided into two types: wet and dry AMD, which is linked with inflammation. Choroidal Neovascularization (CNV) formation or wet AMD is also associated with oxidative stress. Previously, TSP1 has been shown to have a significant alleviating effect on CNV in TSP1 knockout (TSP1-/-) mice. However, the mechanism by which TSP1 ameliorates CNV remains unclear. Here we report that TSP1 reduces nitric oxide production to prevent cells from forming tubes formation and reduced the levels of vascular endothelial growth factor (VEGF) and lipid peroxides (LPO) during oxidative stress. We measured RF/6A cell viability by CCK-8 assay and apoptosis by flow cytometry. RF/6A cell were transfected with TSP1 and STAT3 overexpression, and then the mRNA and protein levels of TSP1 and also the signal pathways were detected by qRT-PCR and Western blot analysis. Migration assays were performed using a transwell system. Co-Immunoprecipitation was used to analyze the binding relationship between CD47 and SHP-2. The results show that overexpression of TSP1 alleviated the damage of oxidative stress to RF/6A cells including increased cell activity and migration, decreased apoptosis and reduced migration compared to the control group. SHP-2 was activated by TSP1 through its receptor CD47 and STAT3 phosphorylation was reduced by activation of SHP-2, thereby blocking STAT3-iNOS pathway and reducing NO concentration in RF/6A cells ultimately protecting them from oxidative stress. Finally, the CNV mice model confirmed that TSP1 overexpression could protect the mice against CNV in vivo, modified the antioxidants levels and decreased the expression of TNF-α and IL-6 under laser irradiation. These results indicate a potential mechanism of TSP1 to slow down formation of CNV in wet AMD, which may bring hope for new treatment strategies.
Asunto(s)
Degeneración Macular/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Factor de Transcripción STAT3/metabolismo , Trombospondina 1/metabolismo , Animales , Apoptosis , Antígeno CD47/metabolismo , Línea Celular , Peroxidación de Lípido , Macaca mulatta , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Transducción de Señal , Trombospondina 1/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Long noncoding RNAs (lncRNAs) have been extensively explored over the past decade, including mice and humans. However, their impact on the transdifferentiation of canine bone marrow mesenchymal stem cells (cBMSCs) into insulin-producing cells (IPCs) is largely unknown. In this study, we used a three-step induction procedure to induce cBMSCs into IPCs, and samples (two biological replicates each) were obtained after each step; the samples consisted of "BMSCs" (B), "stage 1" (S1), "stage 2" (S2), "stage 3" (S3), and "islets" (I). After sequencing, 15,091 lncRNAs were identified, and we screened 110, 41, 23, and 686 differentially expressed lncRNAs (padjusted < 0.05) in B vs. S1, S1 vs. S2, S2 vs. S3, and I vs. S3 pairwise comparisons, respectively. In lncRNA target prediction, there were 166,623 colocalized targets and 2,976,362 correlated targets. Gene Ontology (GO) analysis showed that binding represented the main molecular functions of both the cis- and trans-modes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that the insulin signaling pathway, Rap1 signaling pathway, tight junctions, MAPK signaling pathway, and cell cycle were enriched for these relative genes. The expression of lncRNAs was verified using qRT-PCR. This study provides a lncRNA catalog for future research concerning the mechanism of the transdifferentiation of cBMSCs into IPCs.
Asunto(s)
Genoma/genética , Células Secretoras de Insulina/metabolismo , Insulinas/genética , ARN Largo no Codificante/genética , Animales , Diferenciación Celular/genética , Biología Computacional , Perros , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/genética , Humanos , Insulinas/metabolismo , Células Madre Mesenquimatosas , Ratones , Transducción de Señal/genéticaRESUMEN
This study investigated the profile of circular RNA (circRNA) expression and its epigenetic role associated with human retinoblastoma (RB). Twelve paired primary samples from un-treated RB patients (primary RB samples and corresponding adjacent normal retinal samples) and eight recurrent RB samples from RB patients having recurrence after treatment were collected. Ribosomal-RNA depleted sequencing was performed in four paired primary samples. Quantitative polymerase chain reaction was conducted to validate circRNA and mRNA expression in the other eight paired primary samples and in eight recurrent RB samples. Bioinformatic analysis was applied to predict the oncological signal pathways and the binding microRNA (miRNA) of circRNA. As a result, a total of 47640 circRNAs were identified by RNA-sequencing, with a lower abundance of circRNAs in primary RB samples relative to matched normal retinal samples [22366 (47%) versus 37161 (78%), P <0.001]. Among the 11887 overlapping circRNAs in both RB and normal retinal samples, 550 circRNAs were downregulated and seven were upregulated in primary RB samples compared to normal retinal samples. The host genes of the differentially expressed circRNAs were associated with chromatin modification. TET1-has_circ_0093996 (ten-eleven translocation-1), whose host gene TET1 participates in chromatin modifying, was downregulated in both primary and recurrent RB samples. Programmed cell death 4 ï¼PDCD4) was also downregulated in both primary and recurrent RB samples. We used bioinformatic tools to construct a complete regulatory axis including TET1-has_circ_0093996-miR-183-PDCD4 that regulates RB pathogenesis. In conclusion, circRNA expression is downregulated in RB tumor, which suggests epigenetic regulation of RB pathogenesis by circRNAs.
Asunto(s)
ARN Circular/genética , Neoplasias de la Retina/genética , Retinoblastoma/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Niño , Preescolar , Epigénesis Genética , Femenino , Humanos , Lactante , Masculino , MicroARNs/genética , Proteínas de Unión al ARN/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Neoplasias de la Retina/metabolismo , Retinoblastoma/metabolismo , Análisis de Secuencia de ARN , TranscriptomaRESUMEN
AIM: To describe and analyse the clinical and genetic characteristics of digenic familial exudative vitreoretinopathy (FEVR). METHODS: The study cohort consisted of patients with FEVR (n = 13) to identify patients with two mutations in two different genes. A genetic analysis of the LRP5, FZD4, TSPAN12, and ZNF408 genes was performed with next-generation sequencing (NGS). The genotype data obtained from the patients with FEVR were analysed and correlated with their clinical manifestations. They were then further evaluated in conjunction with other data that were available for these genes. The probands and parents/relatives underwent comprehensive age-appropriate ophthalmic examinations. RESULTS: The medical history and genetic reports of 487 patients with FEVR were reviewed. In all, we identified 13 probands (2.67%, 13/487) with simultaneous mutations in two disease-causing genes. A total of 25 of mutations were found, including10 in FZD4, 8 in LRP5, 3 in ZNF408, 2 in NDP, and 2 in TSPAN12. The most frequent mutations were those in FZD4 and LRP5. We identified 8 mutations that had previously been identified and 17 novel variants. Among 26 eyes, 65.38% exhibited a phenotype, and 10 (38.46%) were stage 4, while 7 (26.92%) were stage 5. CONCLUSIONS: This is the first study to report a group of patients with digenic FEVR. In most affected eyes, the stage was more severe than stage 3. We speculate that the phenotype of FEVR is more severe in patients with digenic rather than monogenic variants of FEVR-related genes.
Asunto(s)
Proteínas de Unión al ADN/genética , Receptores Frizzled/genética , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Mutación , Enfermedades de la Retina/genética , Tetraspaninas/genética , Factores de Transcripción/genética , Peso al Nacer , Niño , Preescolar , Análisis Mutacional de ADN , Enfermedades Hereditarias del Ojo , Vitreorretinopatías Exudativas Familiares , Femenino , Genotipo , Edad Gestacional , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Masculino , Linaje , Fenotipo , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/fisiopatología , Estudios Retrospectivos , Agudeza Visual/fisiología , Adulto JovenRESUMEN
BACKGROUND: Cells respond to DNA damage by activating the phosphatidylinositol-3 kinase-related kinases, p53 and other pathways to promote cell cycle arrest, apoptosis, and/or DNA repair. Here we report that protein palmitoylation, a modification carried out by protein acyltransferases with zinc-finger and Asp-His-His-Cys domains (zDHHC), is required for proper DNA damage responses. RESULTS: Inhibition of protein palmitoylation compromised DNA damage-induced activation of Atm, induction and activation of p53, cell cycle arrest at G2/M phase, and DNA damage foci assembly/disassembly in primary mouse embryonic fibroblasts. Furthermore, knockout of zDHHC16, a palmitoyltransferase gene identified as an interacting protein for c-Abl, a non-receptor tyrosine kinase involved in DNA damage response, reproduced most of the defects in DNA damage responses produced by the inhibition of protein palmitoylation. CONCLUSIONS: Our results revealed critical roles for protein palmitoylation and palmitoyltransferase zDHHC16 in early stages of DNA damage responses and in the regulation of Atm activation.
Asunto(s)
Proteínas Portadoras/metabolismo , Daño del ADN , Reparación del ADN , Aciltransferasas , Animales , Apoptosis , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas Portadoras/genética , Puntos de Control del Ciclo Celular , Células Cultivadas , Femenino , Fibroblastos/citología , Fibroblastos/metabolismo , Eliminación de Gen , Técnicas de Inactivación de Genes , Lipoilación , Ratones Endogámicos C57BL , Mapas de Interacción de Proteínas , Proteínas Proto-Oncogénicas c-abl/metabolismo , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
The microenvironment encompassing a variety of non-malignant cells in close proximity with malignant tumor cells has been well known to significantly affect the behavior of tumor cells. In this study, we therefore studied the mechanism of bone marrow stromal cells in protection of lymphoma cells from spontaneous apoptosis. We demonstrated that adhesion of the freshly isolated lymphoma B cells to bone marrow stromal cells or freshly isolated lymphoma stromal cells inhibited B cell spontaneous apoptosis in culture. This inhibition of apoptosis correlated with decreased cleavage of caspase-3/8 and increased activation of canonical and non-canonical NF-κB signaling pathway. In addition to BAFF signaling which has been reported as a functional determinant for B lymphoma cell survival in the bone marrow environment, we demonstrated RANKL from BMSCs works synergistically with BAFF to activate NF-κB signaling pathway and thus protects lymphoma B cells from spontaneous apoptosis.
Asunto(s)
Regulación Neoplásica de la Expresión Génica/genética , Linfoma de Células B/patología , Células Madre Mesenquimatosas/fisiología , FN-kappa B/fisiología , Proteínas de Neoplasias/fisiología , Transducción de Señal/fisiología , Apoptosis/fisiología , Factor Activador de Células B/antagonistas & inhibidores , Factor Activador de Células B/fisiología , Células Cultivadas , Técnicas de Cocultivo , Humanos , Linfoma de Células B/genética , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Cultivo Primario de Células , Ligando RANK/antagonistas & inhibidores , Ligando RANK/fisiología , Interferencia de ARN , ARN Interferente Pequeño/genética , Células Tumorales Cultivadas , Microambiente TumoralRESUMEN
BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) infection causes severe inflammatory response, respiratory disease and sow reproductive failure. Quercetin is among the widely occurring polypheno found abundantly in nature. Quercetin has anti-inflammatory, anti-oxidative and anti-viral properties. OBJECTIVES: This study aimed to explore the effect and mechanism of quercetin on PRRSV-induced inflammation in MARC-145 cells. METHODS: Observing the cytopathic effect and measurements of inflammatory markers in MARC-145 cells collectively demonstrate that quercetin elicits a curative effect on PRRSV-induced inflammation. Liquid chromatography-mass spectrometry was further used for a non-targeted metabolic analysis of the role of quercetin in the metabolic regulation of PRRSV inflammation in MARC-145 cells. RESULTS: It was shown that quercetin attenuated PRRSV-induced cytopathy in MARC-145 cells. Quercetin treatment inhibited PRRSV replication in MARC-145 cells in a dose-dependent manner. We also found that quercetin inhibited PRRSV-induced mRNA expression and secretion levels of tumour necrosis factor-α, interleukin 1ß and interleukin 6. Metabolomics analysis revealed that quercetin ameliorated PRRSV-induced inflammation. Pathway analysis results revealed that PRRSV-induced pathways including arachidonic acid metabolism, linoleic acid, glycerophospholipid and alanine, aspartate and glutamate metabolism were suppressed by quercetin. Moreover, we confirmed that quercetin inhibited the activation of NF-κB/p65 pathway, probably by attenuating PLA2, ALOX and COX mRNA expression. CONCLUSIONS: These results provide a crucial insight into the molecular mechanism of quercetin in alleviating PRRSV-induced inflammation.
Asunto(s)
Ácido Araquidónico , Glutamina , Inflamación , Virus del Síndrome Respiratorio y Reproductivo Porcino , Quercetina , Quercetina/farmacología , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Virus del Síndrome Respiratorio y Reproductivo Porcino/efectos de los fármacos , Animales , Línea Celular , Inflamación/virología , Inflamación/tratamiento farmacológico , Glutamina/metabolismo , Glutamina/farmacología , Ácido Araquidónico/metabolismo , Porcinos , Síndrome Respiratorio y de la Reproducción Porcina/virología , Síndrome Respiratorio y de la Reproducción Porcina/tratamiento farmacológico , Chlorocebus aethiopsRESUMEN
PURPOSE: Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety. METHODS: A model-based meta-analysis of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-d survival rates. RESULTS: In the study involving 96 articles and 9716 patients, polymyxin B's daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% confidence intervals [CI]: 29.15-38.00) compared to the low-dose group at 35.44% (95% CI: 28.99-41.88), P = 0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI: 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI: 34.75-45.76), P < 0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI: 28.52-30.98), with no significant difference across antibiotic regimens, P = 0.54. The 30-d overall survival rate for monotherapy therapy was 63.6% (95% CI: 59.3-67.5) and 70.2% (95% CI: 64.4-76.2) for association therapy with ß-lactam drugs. CONCLUSIONS: The dosage of polymyxin B does not significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like P. aeruginosa are associated with higher mortality. Combining polymyxin B with other antibiotics, especially ß-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.
RESUMEN
PURPOSE: To develop a technique with clinical 3.0-T magnetic resonance (MR) imaging to delineate local contrast agent distribution in coronary artery walls for potential molecular MR imaging-guided local gene or drug therapy of atherosclerotic coronary artery disease. MATERIALS AND METHODS: This animal protocol was approved by the institutional animal care and use committee and was in compliance with the Guide for the Care and Use of Laboratory Animals. For in vitro confirmation, human arterial smooth muscle cells (SMCs) were used to determine capability of SMCs in uptake of motexafin gadolinium (MGd) and its optimal dose. For ex vivo evaluation, a 2-mL mixture of MGd and trypan blue was locally infused into coronary artery walls of six cadaveric pig hearts with MR monitoring and an MR imaging guidewire, surface coils, or both. For in vivo validation, the balloon catheter was placed into coronary arteries of seven living pigs, and the MGd and trypan blue mixture was infused into arterial walls with MR guidance. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of coronary artery walls were recorded by using different coils between pre- and postcontrast infusion, with subsequent histologic confirmation. Paired Student t tests were used to compare average SNRs and CNRs of arterial walls before and after contrast agent infusion with different coils. RESULTS: SMCs could take up MGd with the optimal concentration at 150 µmol/L. Average SNR with the MR imaging guidewire and surface coil combination was significantly higher than that with the MR imaging guidewire only or with surface coils only (P < .05), and average SNR and CNR of postinfusion MR imaging was significantly higher than that of preinfusion MR imaging (P < .05). Histologic analysis was used to confirm successful intracoronary infiltration of MGd and trypan blue within coronary artery walls. CONCLUSION: MR imaging can be used to delineate locally infused contrast agent distribution in coronary artery walls. This establishes groundwork for development of molecular MR imaging-guided intracoronary therapy.
Asunto(s)
Medios de Contraste/farmacocinética , Vasos Coronarios/metabolismo , Imagen por Resonancia Magnética/métodos , Metaloporfirinas/farmacocinética , Animales , Técnicas In Vitro , Microscopía Confocal , Relación Señal-Ruido , Porcinos , Triptófano/farmacocinéticaRESUMEN
A new fluorescent Zn²âº chemosensor (P1) based on a functionalized porphyrin was synthesized and characterized. P1 displayed dramatic ratiometric variations in absorption and fluorescent emission spectra upon exposure to Zn²âº due to the formation of a 1:1 Zn²âº/P1 complex. The sensor also exhibited high selectivity and sensitivity toward Zn²âº over other common metal ions in the physiological pH range with a detection limit of 1.8 mM. The sensor showed fast response times and excellent reproducibility, thus confirming its potential applicability as a fluorescent sensor for Zn²âº sensing.
Asunto(s)
Técnicas Biosensibles/instrumentación , Porfirinas/química , Zinc/aislamiento & purificación , Fluorescencia , Límite de DetecciónRESUMEN
Introduction: The application of voriconazole in patients with liver dysfunction lacks pharmacokinetic data. In previous study, we proposed to develop voriconazole dosing regimens for these patients according to their total bilirubin, but the regimens are based on Monte Carlo simulation and has not been further verified in clinical practice. Besides, there are few reported factors that significantly affect the efficacy of voriconazole. Methods: We collected the information of patients with liver dysfunction hospitalized in our hospital from January 2018 to May 2022 retrospectively, including their baseline information and laboratory data. We mainly evaluated the efficacy of voriconazole and the target attainment of voriconazole trough concentration. Results: A total of 157 patients with liver dysfunction were included, from whom 145 initial and 139 final voriconazole trough concentrations were measured. 60.5% (95/157) of patients experienced the adjustment of dose or frequency. The initial voriconazole trough concentrations were significantly higher than the final (mean, 4.47 versus 3.90 µg/mL, p = 0.0297). Furthermore, daily dose, direct bilirubin, lymphocyte counts and percentage, platelet, blood urea nitrogen and creatinine seven covariates were identified as the factors significantly affect the voriconazole trough concentration. Binary logistic regression analysis revealed that the lymphocyte percentage significantly affected the efficacy of voriconazole (OR 1.138, 95% CI 1.016-1.273), which was further validated by the receiver operating characteristic curve. Conclusion: The significant variation in voriconazole trough concentrations observed in patients with liver dysfunction necessitates caution when prescribing this drug. Clinicians should consider the identified factors, particularly lymphocyte percentage, when dosing voriconazole in this population.
RESUMEN
BACKGROUND: Super-selected intra-arterial chemotherapy has increasingly been used as conservative management for retinoblastoma during the past decade. However, the absence of evidence from randomised controlled trials engendered controversy in the administration route of chemotherapy. We aimed to assess the efficacy and safety of intra-arterial chemotherapy compared with intravenous chemotherapy. METHODS: This open-label, multicentre, randomised trial was done at six hospitals in China. Patients with new-onset unilateral group D or E retinoblastoma (poorly defined, large, or very large tumours, according to the International Intraocular Retinoblastoma Classification) without high-risk clinical factors were included. Patients were randomly assigned (1:1) to receive intra-arterial chemotherapy (injections of 0·5 mg/kg [or depending on age] melphalan with 20 mg carboplatin [first and third cycles] or with 1 mg topotecan [second and fourth cycles]) or intravenous chemotherapy (0·05 mg/kg [or 1·5 mg/m2] vincristine, 5 mg/kg [or 150 mg/m2] etoposide, and 18·6 mg/kg [or 560 mg/m2] carboplatin for six cycles). After intra-arterial chemotherapy, patients received a subcutaneous injection of 0·1 mL nadroparin calcium twice at a 12 h interval. Both intra-arterial and intravenous chemotherapy cycles were completed every 4 weeks. No masking was done, except of independent statisticians, who were masked to the allocation information. The primary outcome was 2-year progression-free globe salvage rate, defined as the time from randomisation to tumour progression or enucleation, whichever occurred first, and was analysed by intention to treat. We also recorded predefined safety outcomes (myelosuppression and ophthalmic arterial stenosis or occlusion) and severe adverse events likely to be related to study treatment. The study is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-15006469, and is complete. FINDINGS: Between June 1, 2015, and June 1, 2018, 234 patients with newly diagnosed retinoblastoma were screened and 143 eligible patients (median age 23·6 months [IQR 14·0-31·9]) were enrolled and randomly assigned to the intra-arterial chemotherapy group (n=72) or the intravenous chemotherapy group (n=71). At a median follow-up of 35·8 months (IQR 28·4-43·0), the 2-year progression-free globe salvage rate was 53% (38 of 72 patients) in the intra-arterial chemotherapy group and 27% (19 of 71 patients) in the intravenous chemotherapy group (risk ratio 1·97, 95% CI 1·27-3·07, p=0·0020). Myelosuppression was less common in the intra-arterial chemotherapy group than in the intravenous chemotherapy group (37 [51%] of 72 patients vs 50 [70%] of 71 patients; 0·73, 95% CI 0·56-0·96, p=0·021) and less severe (ptrend=0·0070). In the intra-arterial chemotherapy group, two (3%) of 72 patients had ophthalmic artery occlusion and 13 (18%) patients had ophthalmic artery stenosis. INTERPRETATION: Our findings show that intra-arterial chemotherapy could significantly improve the globe salvage rate in children with advanced unilateral retinoblastoma compared with intravenous chemotherapy, with mild systemic complications and no difference in overall survival rate. Intra-arterial chemotherapy could be an acceptable first-line treatment in children with advanced unilateral retinoblastoma. FUNDING: Scientific Research Program of the National Health and Family Planning Commission of China, the Clinical Research Plan of Shanghai Hospital Development Center, the National Natural Science Foundation of China, and the Science and Technology Commission of Shanghai Municipality.
Asunto(s)
Neoplasias de la Retina , Retinoblastoma , Humanos , Niño , Lactante , Preescolar , Retinoblastoma/tratamiento farmacológico , Retinoblastoma/inducido químicamente , Carboplatino/efectos adversos , Constricción Patológica/inducido químicamente , China , Neoplasias de la Retina/tratamiento farmacológico , Neoplasias de la Retina/inducido químicamente , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Solar-driven steam generation (SSG) is regarded as a feasible solution to the problem of fresh water scarcity. Although several attempts have been devoted to increase the efficiency of solar-to-steam conversion, it remains difficult to fabricate cost-effective, steady, and multi-angle sunlight-absorbing evaporators from readily available biomass materials. Herein, a novel hierarchical structured SSG evaporator (PDA@Shell-NaClO) is developed through a simple, low-cost, and scalable etching treatment on discarded sea urchin (SU) shells. Attributing to the dedicatedly designed microneedles array structure and porous skeleton structure of the SU shell, this PDA@Shell-NaClO evaporator shows an outstanding average light absorption performance (>90%) in a broad range of angles from 0° to 60° and exceedingly high evaporation rate of 2.81 kg m-2 h-1 under one sun condition. Furthermore, the prepared evaporator also maintains an overall stable evaporation performance and exhibits an excellent durability for a long time of up to two weeks in actual seawater. This full-ocean biomass-based SSG evaporator with plentiful raw material availability offers innovative opportunities for large-scale fresh water production.