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1.
Nature ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39322664

RESUMEN

Despite a high response rate in chimeric antigen receptor (CAR) T cell therapy for acute lymphocytic leukaemia (ALL)1-3, approximately 50% of patients relapse within the first year4-6, representing an urgent question to address in the next stage of cellular immunotherapy. Here, to investigate the molecular determinants of ultralong CAR T cell persistence, we obtained a single-cell multi-omics atlas from 695,819 pre-infusion CAR T cells at the basal level or after CAR-specific stimulation from 82 paediatric patients with ALL enrolled in the first two CAR T ALL clinical trials and 6 healthy donors. We identified that elevated type 2 functionality in CAR T infusion products is significantly associated with patients maintaining a median B cell aplasia duration of 8.4 years. Analysis of ligand-receptor interactions revealed that type 2 cells regulate a dysfunctional subset to maintain whole-population homeostasis, and the addition of IL-4 during antigen-specific activation alleviates CAR T cell dysfunction while enhancing fitness at both transcriptomic and epigenomic levels. Serial proteomic profiling of sera after treatment revealed a higher level of circulating type 2 cytokines in 5-year or 8-year relapse-free responders. In a leukaemic mouse model, type 2high CAR T cell products demonstrated superior expansion and antitumour activity, particularly after leukaemia rechallenge. Restoring antitumour efficacy in type 2low CAR T cells was attainable by enhancing their type 2 functionality, either through incorporating IL-4 into the manufacturing process or by priming manufactured CAR T products with IL-4 before infusion. Our findings provide insights into the mediators of durable CAR T therapy response and suggest potential therapeutic strategies to sustain long-term remission by boosting type 2 functionality in CAR T cells.

2.
EMBO J ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39242788

RESUMEN

Monoamine neurotransmitters generated by de novo synthesis are rapidly transported and stored into synaptic vesicles at axon terminals. This transport is essential both for sustaining synaptic transmission and for limiting the toxic effects of monoamines. Here, synthesis of the monoamine histamine by histidine decarboxylase (HDC) and subsequent loading of histamine into synaptic vesicles are shown to be physically and functionally coupled within Drosophila photoreceptor terminals. This process requires HDC anchoring to synaptic vesicles via interactions with N-ethylmaleimide-sensitive fusion protein 1 (NSF1). Disassociating HDC from synaptic vesicles disrupts visual synaptic transmission and causes somatic accumulation of histamine, which leads to retinal degeneration. We further identified a proteasome degradation system mediated by the E3 ubiquitin ligase, purity of essence (POE), which clears mislocalized HDC from the soma, thus eliminating the cytotoxic effects of histamine. Taken together, our results reveal a dual mechanism for translocation and degradation of HDC that ensures restriction of histamine synthesis to axonal terminals and at the same time rapid loading into synaptic vesicles. This is crucial for sustaining neurotransmission and protecting against cytotoxic monoamines.

3.
Mol Cell ; 80(6): 1055-1066.e6, 2020 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-33188728

RESUMEN

The causative virus of the COVID-19 pandemic, SARS-CoV-2, uses its nonstructural protein 1 (Nsp1) to suppress cellular, but not viral, protein synthesis through yet unknown mechanisms. We show here that among all viral proteins, Nsp1 has the largest impact on host viability in the cells of human lung origin. Differential expression analysis of mRNA-seq data revealed that Nsp1 broadly alters the cellular transcriptome. Our cryo-EM structure of the Nsp1-40S ribosome complex shows that Nsp1 inhibits translation by plugging the mRNA entry channel of the 40S. We also determined the structure of the 48S preinitiation complex formed by Nsp1, 40S, and the cricket paralysis virus internal ribosome entry site (IRES) RNA, which shows that it is nonfunctional because of the incorrect position of the mRNA 3' region. Our results elucidate the mechanism of host translation inhibition by SARS-CoV-2 and advance understanding of the impacts from a major pathogenicity factor of SARS-CoV-2.


Asunto(s)
COVID-19/metabolismo , Biosíntesis de Proteínas , ARN Mensajero/metabolismo , ARN Viral/metabolismo , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidad , Proteínas no Estructurales Virales/metabolismo , Animales , COVID-19/genética , COVID-19/patología , Chlorocebus aethiops , Microscopía por Crioelectrón , Humanos , ARN Mensajero/genética , ARN Viral/genética , Subunidades Ribosómicas Pequeñas de Eucariotas/genética , Subunidades Ribosómicas Pequeñas de Eucariotas/metabolismo , Subunidades Ribosómicas Pequeñas de Eucariotas/ultraestructura , Subunidades Ribosómicas Pequeñas de Eucariotas/virología , SARS-CoV-2/genética , SARS-CoV-2/ultraestructura , Células Vero , Proteínas no Estructurales Virales/genética
4.
BMC Plant Biol ; 24(1): 22, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38166716

RESUMEN

BACKGROUND: Floral patterns are crucial for insect pollination and plant reproduction. Generally, once these patterns are established, they exhibit minimal changes under natural circumstances. However, the Clematis cultivar' Vyvyan Pennell', the apetalous lineage in the Ranunculaceae family, produces two distinct types of flowers during different seasons. The regulatory mechanism responsible for this phenomenon remains largely unknown. In this study, we aim to shed light on this floral development with shifting seasonal patterns by conducting extensive morphological, transcriptomic, and hormone metabolic analyses. Our findings are anticipated to contribute valuable insights into the diversity of flowers in the Ranunculaceae family. RESULTS: The morphological analysis revealed that the presence of extra petaloid structures in the spring double perianth was a result of the transformation of stamens covered with trichomes during the 5th developmental stage. A de novo reference transcriptome was constructed by comparing buds and organs within double and single perianth from both seasons. A total of 209,056 unigenes were assembled, and 5826 genes were successfully annotated in all six databases. Among the 69,888 differentially expressed genes from the comparative analysis, 48 genes of utmost significance were identified. These critical genes are associated with various aspects of floral development. Interestingly, the A-, B-, and C-class genes exhibited a wider range of expression and were distinct within two seasons. The determination of floral organ identity was attributed to the collaborative functioning of all the three classes genes, aligning with a modified "fading border model". The phytohormones GA3, salicylic acid, and trans-zeatin riboside may affect the formation of the spring double perianth, whereas GA7 and abscisic acid may affect single flowers in autumn. CONCLUSIONS: We presumed that the varying temperatures between the two seasons served as the primary factor in the alteration of floral patterns, potentially affecting the levels of plant hormones and expressions of organ identity genes. However, a more thorough investigation is necessary to fully comprehend the entire regulatory network. Nonetheless, our study provides some valuable informations for understanding the underlying mechanism of floral pattern alterations in Clematis.


Asunto(s)
Clematis , Estaciones del Año , Clematis/genética , Clematis/metabolismo , Perfilación de la Expresión Génica , Transcriptoma , Flores , Reguladores del Crecimiento de las Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas
5.
New Phytol ; 242(2): 641-657, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38379453

RESUMEN

Nitrate is the main source of nitrogen (N) available to plants and also is a signal that triggers complex regulation of transcriptional networks to modulate a wide variety of physiological and developmental responses in plants. How plants adapt to soil nitrate fluctuations is a complex process involving a fine-tuned response to nitrate provision and N starvation, the molecular mechanisms of which remain largely uncharted. Here, we report that the wheat transcription factor TaLBD41 interacts with the nitrate-inducible transcription factor TaNAC2 and is repressed by nitrate provision. Electrophoretic mobility shift assay and dual-luciferase system show that the TaLBD41-NAC2 interaction confers homeostatic coordination of nitrate uptake, reduction, and assimilation by competitively binding to TaNRT2.1, TaNR1.2, and TaNADH-GOGAT. Knockdown of TaLBD41 expression enhances N uptake and assimilation, increases spike number, grain yield, and nitrogen harvest index under different N supply conditions. We also identified an elite haplotype of TaLBD41-2B associated with increased spike number and grain yield. Our study uncovers a novel mechanism underlying the interaction between two transcription factors in mediating wheat adaptation to nitrate availability by antagonistically regulating nitrate uptake and assimilation, providing a potential target for designing varieties with efficient N use in wheat (Triticum aestivum).


Asunto(s)
Nitratos , Nitrógeno , Nitratos/metabolismo , Nitrógeno/metabolismo , Transporte Biológico , Grano Comestible/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
6.
Ann Surg Oncol ; 31(6): 3887-3893, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38472675

RESUMEN

BACKGROUND: The rise of artificial intelligence (AI) in medicine has revealed the potential of ChatGPT as a pivotal tool in medical diagnosis and treatment. This study assesses the efficacy of ChatGPT versions 3.5 and 4.0 in addressing renal cell carcinoma (RCC) clinical inquiries. Notably, fine-tuning and iterative optimization of the model corrected ChatGPT's limitations in this area. METHODS: In our study, 80 RCC-related clinical questions from urology experts were posed three times to both ChatGPT 3.5 and ChatGPT 4.0, seeking binary (yes/no) responses. We then statistically analyzed the answers. Finally, we fine-tuned the GPT-3.5 Turbo model using these questions, and assessed its training outcomes. RESULTS: We found that the average accuracy rates of answers provided by ChatGPT versions 3.5 and 4.0 were 67.08% and 77.50%, respectively. ChatGPT 4.0 outperformed ChatGPT 3.5, with a higher accuracy rate in responses (p < 0.05). By counting the number of correct responses to the 80 questions, we then found that although ChatGPT 4.0 performed better (p < 0.05), both versions were subject to instability in answering. Finally, by fine-tuning the GPT-3.5 Turbo model, we found that the correct rate of responses to these questions could be stabilized at 93.75%. Iterative optimization of the model can result in 100% response accuracy. CONCLUSION: We compared ChatGPT versions 3.5 and 4.0 in addressing clinical RCC questions, identifying their limitations. By applying the GPT-3.5 Turbo fine-tuned model iterative training method, we enhanced AI strategies in renal oncology. This approach is set to enhance ChatGPT's database and clinical guidance capabilities, optimizing AI in this field.


Asunto(s)
Inteligencia Artificial , Carcinoma de Células Renales , Neoplasias Renales , Humanos , Neoplasias Renales/patología , Carcinoma de Células Renales/patología , Pronóstico
7.
Opt Express ; 32(10): 16722-16731, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38858871

RESUMEN

This work reports the nonlinear dynamics of a mid-infrared interband cascade laser (ICL) subject to optical injection. It is shown that the stable locking regime is asymmetric and broadens with increasing injection strength. Outside the locking regime, the ICL mostly produces period-one oscillations. However, three categories of periodic pulse oscillations are observed in the vicinity of the Hopf bifurcation and the saddle-node bifurcation. In particular, it is found that the ICL generates broadband chaos at a near-threshold pump current, and the chaos bandwidth is over 300 MHz.

8.
Opt Lett ; 49(11): 3142-3145, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824348

RESUMEN

Near-infrared semiconductor lasers subject to optical feedback usually produce chaos with a broad bandwidth of a few GHz. However, the reported mid-infrared interband cascade lasers (ICLs) only show chaos with a limited bandwidth below 1 GHz. Here we show that an ICL with optical feedback is able to generate broadband chaos as well. The mid-infrared chaos exhibits a remarkable bandwidth of about 6 GHz, which is comparable to that of the near-infrared counterpart. In addition, the spectral coverage in the electrical domain reaches as high as 17.7 GHz. It is found that the chaos bandwidth generally broadens with increasing feedback ratio and/or increasing pump current of the laser, while it is insensitive to the feedback length.

9.
Diabetes Obes Metab ; 26(11): 4976-4988, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39228281

RESUMEN

AIM: Low birthweight is an issue during pregnancy associated with an increased risk of developing liver disease later in life. Previous Mendelian randomisation (MR) studies which explored this issue have not isolated the direct impact of the foetus on birthweight. In the present study, MR was used to assess whether direct foetal effects on birthweight were causally associated with liver structure, function and disease risk independent of intrauterine effects. MATERIALS AND METHODS: We extracted single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) about direct foetal-affected birthweight (321 223 cases) to conduct univariable and multivariable MR analyses to explore the relationships between birthweight and 4 liver structure measures, 9 liver function measures and 18 liver diseases. A two-step MR analysis was used to further assess and quantify the mediating effects of the mediators. RESULTS: When isolating direct foetal effects, genetically predicted lower birthweight was associated with a higher risk of non-alcoholic fatty liver disease (NAFLD) (odds ratios [OR], 95% confidence interval [CI]: 1.61, 1.29-2.02, p < 0.001), higher magnetic resonance imaging [MRI] proton density fat fraction (PDFF) and higher serum gamma glutamyltransferase (GGT). Two-step MR identified two candidate mediators that partially mediate the direct foetal effect of lower birthweight on NAFLD, including fasting insulin (proportion mediated: 22.29%) and triglycerides (6.50%). CONCLUSIONS: Our MR analysis reveals a direct causal association between lower birthweight and liver MRI PDFF, as well as the development of NAFLD, which persisted even after accounting for the potential influence of maternal factors. In addition, we identified fasting insulin and triglycerides as mediators linking birthweight and hepatic outcomes, providing insights for early clinical interventions.


Asunto(s)
Peso al Nacer , Estudio de Asociación del Genoma Completo , Hígado , Análisis de la Aleatorización Mendeliana , Enfermedad del Hígado Graso no Alcohólico , Polimorfismo de Nucleótido Simple , Humanos , Femenino , Embarazo , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/genética , Factores de Riesgo , Imagen por Resonancia Magnética , Recién Nacido de Bajo Peso , Masculino , Recién Nacido , gamma-Glutamiltransferasa/sangre
10.
Eur J Nutr ; 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38847866

RESUMEN

BACKGROUND: Antioxidant and pro-oxidant dietary patterns and lifestyle changes have been considered to play a crucial role in Helicobacter pylori (H. pylori) infection. We conducted this study to investigate the underlying association between oxidative balance score (OBS) and H. pylori infection in the US population. METHODS: This was a cross-sectional study according to data from the National Health and Nutrition Examination Survey (1999-2000), and included individuals with complete information about dietary intake and H. pylori serologic testing results. In the present study, we used multivariate logistic regression analysis, smoothed curve fitting, subgroup analyses, and Cox proportional hazards modeling based on demographic and clinical variables to examine the relationship between OBS and H. pylori infection. RESULTS: A total of 3413 individuals participated in our analysis with an average age of 32.31 years. The prevalence of H. pylori infection in the study population was 29.77%. By performing smooth curve fitting analysis, we observed an approximately linear relationship between OBS and H. pylori infection, indicating that lower OBS was associated with higher risk of H. pylori infection, especially in over 60 years of age and non-Hispanic white populations. All-cause mortality was also found lower in individuals with higher OBS levels. CONCLUSION: In the US population, increased levels of OBS were associated with a reduced risk of H. pylori infection and decreased all-cause mortality. More and further work is still needed to elucidate the precise mechanism of the association between OBS and H. pylori infection.

11.
Cell Biochem Funct ; 42(3): e4017, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38603595

RESUMEN

Chromosomal instability (CIN), caused by errors in the segregation of chromosomes during mitosis, is a hallmark of many types of cancer. The fidelity of chromosome segregation is governed by a sophisticated cellular signaling network, one crucial orchestrator of which is Heterochromatin protein 1 (HP1). HP1 dynamically localizes to distinct sites at various stages of mitosis, where it regulates key mitotic events ranging from chromosome-microtubule attachment to sister chromatid cohesion to cytokinesis. Our evolving comprehension of HP1's multifaceted role has positioned it as a central protein in the orchestration of mitotic processes.


Asunto(s)
Homólogo de la Proteína Chromobox 5 , Mitosis
12.
Ecotoxicol Environ Saf ; 285: 117135, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39353379

RESUMEN

BACKGROUND: Hypoxia caused by global climate change and human activities has become a growing concern eliciting serious effect and damages to aquatic animals. Hexagrammos otakii is usually a victim of hypoxia which caused by high density aquaculture and high nutrient input. The mechanism underlying ferroptosis regulation after hypoxia-stress in liver of H. otakii, however, remains elusive. METHODS: For a duration of 15 days, expose the H. otakii to low concentrations of dissolved oxygen (3.4 ± 0.2 mg/L). Detecting alterations in the H. otakii liver tissue by chemical staining, immunohistochemistry, and electron microscopy. The expression variations of relevant genes in the liver of the H. otakii were simultaneously detected using Western blot and qPCR. A correlation analysis was performed between HIF-1α and iron ion expression in the liver of H. otakii following hypoxic stress. RESULTS: In this study, we conducted the whole ferroptosis integrated analysis of H. otakii under chronic hypoxic condition. Reactive oxygen species (ROS) are highly accumulated under the hypoxia treatment (Superoxide Dismutase, SOD; Catalase, CAT), and which results in a significantly enhanced of lipid peroxidation (Lipid Peroxidation, LPO; Malondialdehyde, MDA; Aminotransferase, AST; Alanine aminotransferase, ALT) in liver tissue. The HIF-1α signaling is activated to cope with the hypoxia stress through strategies including changing iron ion concentration (Fe3+ and TFR1) to breaking the oxidation balance (GSH and GSH-Px), and enhancing ferroptosis gene expression (GPX4). The expression of genes related to ferroptosis pathway (DMT1, FTH1, STEAP3, ACSL4, γ-GCS, SLC7A11) is significantly upregulated and associated to the expression of iron and HIF-1α. CONCLUSIONS: It is demonstrated that the HIF-1α/Fe3+/ROS/GPX4 axis is involved in promoting ferroptosis in fat greening hepatocytes following hypoxia-stress. Ultimately, our findings unveil a process by which hypoxic stress strongly encourages ferroptosis by triggering HIF-1α and boosting iron synthesis.

13.
J Environ Manage ; 370: 122807, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39368390

RESUMEN

Phytoremediation is an efficient technology for the removal of herbicide atrazine (ATZ) contamination in water bodies, but its ability to reduce ATZ under combined pollution remains unclear, especially ATZ co-existing with the emerging pollutant graphene oxide (GO) that may have potential effects on ATZ fate, plants and microbes. Herein, we investigated the phytoremediation potential of an emergent plant (Iris pseudacorus) for ATZ and the response of bacteria in a hydroponic system with and without GO. The results showed that plants enhanced ATZ dissipation in water with the increased removal rate by a factor of 1.7-4.0. GO restricted ATZ uptake by plants, but favored ATZ bioconcentration in cell walls. The plant contributed most to changes in the bacterial communities, decreasing the alpha diversity, while enriching the functional categories involving in amino acid and carbohydrate metabolisms. These findings indicated that I. pseudacorus can be employed as an effective candidate of phytoremediation for ATZ co-existing with GO at environmentally relevant concentrations, tending to recruit bacteria with plant stress tolerance and growth-promotion activities more than with ATZ degradation activities; GO exerted a mitigating effect on ATZ stress improving the barrier function of cell walls, but decreased the contribution of plants to ATZ removal.

14.
J Sci Food Agric ; 104(10): 5944-5954, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38415770

RESUMEN

BACKGROUND: Soy 11S globulin has high thermal stability, limiting its application in the production of low-temperature gel foods. In this study, the low-frequency magnetic field (LF-MF, 5 mT) treatment (time, 30, 60, 90, and 120 min) was used to improve the solubility, conformation, physicochemical properties, surface characteristics, and gel properties of soy 11S globulin. RESULTS: Compared with the native soy 11S globulin, the sulfhydryl content, emulsifying capacity, gel strength, water-holding capacity, and absolute zeta potential values significantly increased (P < 0.05) after LF-MF treatment. The LF-MF treatment induced the unfolding of the protein structure and the fracture of disulfide bonds. The variations in solubility, foaming properties, viscosity, surface hydrophobicity, and rheological properties were closely related to the conformational changes of soy 11S globulin, with the optimum LF-MF modification time being 90 min. CONCLUSION: LF-MF treatment is an effective method to improve various functional properties of native soy 11S globulin, and this study provides a reference for the development of plant-based proteins in the food industry. © 2024 Society of Chemical Industry.


Asunto(s)
Globulinas , Glycine max , Interacciones Hidrofóbicas e Hidrofílicas , Campos Magnéticos , Reología , Solubilidad , Proteínas de Soja , Proteínas de Soja/química , Viscosidad , Globulinas/química , Glycine max/química , Conformación Proteica
15.
BMC Nurs ; 23(1): 427, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918825

RESUMEN

BACKGROUND: The accurate diagnosis and effective management of arrhythmias are crucial, with nurses playing a key role in the early detection and treatment, significantly impacting patient outcomes. Improving education on arrhythmias among nurses, especially in critical care and perioperative settings, can enhance patient safety and the quality of care. METHODS: A total of 116 trainee nurses were randomly divided into two groups: one utilizing the conceive-design-implement-operate (CDIO) model and the other employing a traditional lecture-based learning (LBL) method, to undergo arrhythmia training. The studyassessed the effects of the two teaching methods and investigated the students' attitudes toward these educational practices, with all participants completing pre- and post-course tests. RESULTS: The CDIO model significantly enhances nursing students' arrhythmia proficiency, yielding higher test scores and sustained improvement after 24-week compared to the traditional LBL method, alongside markedly better self-learning enthusiasm, understanding, satisfaction with the teaching approach and effectiveness, and interest in learning arrhythmia. The CDIO model in nursing arrhythmia courses boosts theoretical knowledge and application, showing potential in clinical skill enhancement. CONCLUSIONS: Our study introduces the CDIO model in nursing arrhythmia courses, with improvement in knowledge and skills, and promise for broader application.

16.
BMC Nurs ; 23(1): 702, 2024 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-39343940

RESUMEN

BACKGROUND: Occupational Bloodborne Exposures (OBEs) are incidents where healthcare workers come into contact with blood or other potentially infectious materials, leading to risks of transmitting bloodborne pathogens. Nursing students, often in direct contact with patients, face heightened risks due to their duties. METHODS: First, we conducted a cross-sectional survey using a OBEs questionnaire to explore the knowledge, attitudes, practices, and needs regarding OBEs among nursing students. Subsequently, we used a randomized controlled trial (RCT) to compare the impact of the Presentation-Assimilation-Discussion (PAD) method with the traditional lecture-based learning (LBL) method on OBEs education for nursing students. Pre-test, post-test, and retention test were used to observe the teaching effectiveness, and the students' feedback on the teaching method was also observed. RESULTS: In the cross-sectional survey, we found that nursing students lacked sufficient knowledge and management skills regarding OBEs but recognized the importance of standard precautions and expressed a desire for systematic OBEs training during their education and internships. In the RCT, the total, theoretical, and practical scores of the PAD and LBL groups were comparable in the pre-test (56.70 ± 3.47 vs. 56.40 ± 3.95, 33.09 ± 3.39 vs. 33.33 ± 2.44, 23.61 ± 4.66 vs. 23.07 ± 4.84, p > 0.05). After training, the PAD model demonstrated an advantage over the LBL model in immediate total (84.25 ± 4.06 vs. 78.95 ± 4.23, p < 0.001), theoretical (54.32 ± 2.43 vs. 51.44 ± 2.58, p < 0.001), and practical scores (29.93 ± 3.90 vs. 27.51 ± 4.33, p < 0.01). It also showed superior retention of total (69.05 ± 3.87 vs. 65.77 ± 2.94, p < 0.001) and theoretical scores (39.05 ± 3.05 vs. 36.23 ± 3.18, p < 0.001). However, there was no significant difference in the retention of practical scores between the two groups (30.00 ± 4.76 vs. 29.53 ± 3.73, p > 0.05). The PAD group benefited more across various learning dimensions but reported a higher study load. CONCLUSIONS: Our study reveals that the PAD model could be a valuable approach for teaching OBEs to nursing students.

17.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2047-2063, 2024 Apr.
Artículo en Zh | MEDLINE | ID: mdl-38812222

RESUMEN

Nauclea officinalis is a Chinese medicinal material with a high medicinal value, which contains various chemical constituents such as alkaloids, pentacyclic triterpenoids and their saponins, organic phenolic acids and their glycosides, iridoids, and flavonoids. It has antiviral, antibacterial, antipyretic, analgesic, anti-inflammatory, and immunoregulatory functions. This article systematically reviewed the reported chemical constituents and pharmacological effects of N. officinalis. According to the concept of quality markers, the quality markers of N. officinalis were predicted and analyzed from the aspects of plant kinship, specificity of chemical constituents, traditional drug efficacy, measurability of chemical constituents, plasma components, and different producing areas and harvest times, in order to provide a basis for the quality evaluation of N. officinalis.


Asunto(s)
Medicamentos Herbarios Chinos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Humanos , Animales , Rubiaceae/química , Control de Calidad
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(2): 188-193, 2024 Feb 15.
Artículo en Zh | MEDLINE | ID: mdl-38436318

RESUMEN

OBJECTIVES: To study the in vitro expression of three phenylalanine hydroxylase (PAH) mutants (p.R243Q, p.R241C, and p.Y356X) and determine their pathogenicity. METHODS: Bioinformatics techniques were used to predict the impact of PAH mutants on the structure and function of PAH protein. Corresponding mutant plasmids of PAH were constructed and expressed in HEK293T cells. Quantitative reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the three PAH mutants, and their protein levels were assessed using Western blot and enzyme-linked immunosorbent assay. RESULTS: Bioinformatics analysis predicted that all three mutants were pathogenic. The mRNA expression levels of the p.R243Q and p.R241C mutants in HEK293T cells were similar to the mRNA expression level of the wild-type control (P>0.05), while the mRNA expression level of the p.Y356X mutant significantly decreased (P<0.05). The PAH protein expression levels of all three mutants were significantly reduced compared to the wild-type control (P<0.05). The extracellular concentration of PAH protein was reduced in the p.R241C and p.Y356X mutants compared to the wild-type control (P<0.05), while there was no significant difference between the p.R243Q mutant and the wild type control (P>0.05). CONCLUSIONS: p.R243Q, p.R241C and p.Y356X mutants lead to reduced expression levels of PAH protein in eukaryotic cells, with p.R241C and p.Y356X mutants also affecting the function of PAH protein. These three PAH mutants are to be pathogenic.


Asunto(s)
Fenilalanina Hidroxilasa , Humanos , Células HEK293 , Fenilalanina Hidroxilasa/genética , Western Blotting , Biología Computacional , ARN Mensajero
19.
Prostate ; 83(1): 3-15, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36131555

RESUMEN

BACKGROUND: To compare the safety and clinical efficacy of Moses laser enucleation of the prostate (MoLEP) with those of holmium laser enucleation of the prostate (HoLEP) for treating benign prostatic hyperplasia (BPH). METHODS: We systematically searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang databases, and SinoMed databases. The retrieval period was from the establishment of the database to March 2022. Stata17.0 was used for calculations and statistical analyses. RESULTS: This study included 12 articles comprising 1160 patients for meta-analysis. Compared with those of the HoLEP group, the hemostasis time (weighted mean difference [WMD] = -4.66, 95% confidence interval [CI] [-6.47, -2.84], p < 0.001), enucleation time (WMD = -7.23, 95% CI [-10.67, -3.79], p < 0.001), operative time (WMD = -15.02, 95% CI [-20.50, -9.53], p< 0.001), length of hospital stay (WMD = -15.02, 95% CI [-20.50, -9.53], p< 0.001), intraoperative blood loss (WMD = -11.19, 95% CI [-12.94, -9.44], p< 0.001), and total postoperative complications rate (OR = 0.51, 95% CI [0.32, 0.81], p = 0.004) were shorter in the MoLEP group. Postoperative quality of life (WMD = 0.30, 95% CI [0.00, 0.59], p = 0.047) was lower in the HoLEP group, and there were no statistically significant differences in the International Prostate Symptom Score, postoperative maximum urinary flow rate, and postoperative residual urine (p > 0.05). CONCLUSION: MoLEP has more advantages than HoLEP in terms of safety, shorter operation time and hospital stay, and fewer complications. However, this conclusion needs to be verified with a larger sample size, longer follow-up time, and multicenter randomized controlled trial data.


Asunto(s)
Holmio , Láseres de Estado Sólido , Masculino , Humanos , Láseres de Estado Sólido/uso terapéutico , Próstata/cirugía , Calidad de Vida , Tecnología , Estudios Multicéntricos como Asunto
20.
Ann Surg Oncol ; 30(6): 3805-3816, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36879036

RESUMEN

BACKGROUND: For medical institutions without robotic equipment, it remains uncertain whether laparoscopic radical nephroureterectomy (LNU) can achieve results similar to those of robotic surgery for the treatment of upper tract urothelial carcinoma (UTUC). This meta-analysis aimed to compare the efficacy and safety of robot-assisted radical nephroureterectomy (RANU) with that of LNU using a large sample size of patients. METHODS: A systematic meta-analysis was performed using data (available to May 2022) acquired from multiple scientific databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Assessing the Methodological Quality of Systematic Reviews (AMSTAR) guidelines, according to the protocols registered with PROSPERO (CRD42021264046), were followed to perform this cumulative analysis. RESULTS: Nine high-quality studies were included in this analysis, considering factors such as operative time (OT), estimated blood loss (EBL), length of hospital stay (LOS), positive surgical margins (PSM), and complications. Statistical indicators revealed no significant differences between the RANU and LNU groups in terms of OT (weighted mean difference [WMD] 29.41, 95% confidence interval [CI] -1.10 to 59.92; p = 0.22), EBL (WMD -55.30, 95% CI -171.14 to 60.54; p = 0.13), LOS (WMD -0.39, 95% CI -1.03 to 0.25; p = 0.12), PSM (odds ratio [OR] 1.22, 95% CI 0.44-3.36; p = 0.17], or complications (OR 0.91, 95% CI 0.49-1.69; p = 0.13). CONCLUSION: The meta-analysis showed that the perioperative and safety indicators of both RANU and LNU were similar and both showed favorable outcomes in UTUC treatment. However, some uncertainties remain in the implementation and selection of lymph nodes for dissection.


Asunto(s)
Carcinoma de Células Transicionales , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Robótica , Neoplasias de la Vejiga Urinaria , Humanos , Nefroureterectomía/efectos adversos , Carcinoma de Células Transicionales/cirugía , Carcinoma de Células Transicionales/patología , Procedimientos Quirúrgicos Robotizados/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias de la Vejiga Urinaria/cirugía , Resultado del Tratamiento , Laparoscopía/efectos adversos , Laparoscopía/métodos
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