Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.309
Filtrar
1.
J Clin Exp Hepatol ; 15(1): 102409, 2025.
Artículo en Inglés | MEDLINE | ID: mdl-39391324

RESUMEN

Backgrounds and aim: Viscoelastic tests (VET) like rotational thromboelastometry (ROTEM) assess global hemostasis in cirrhosis. We aimed to assess whether ROTEM-guided blood product transfusion results in lower blood product requirements in patients with cirrhosis undergoing elective invasive procedures as compared to standard of care (SOC) based on conventional coagulation test (CCT). Methods: In this open label randomized controlled trial, patients with cirrhosis and abnormal CCT who were undergoing an invasive procedure were randomized to receive blood products either by ROTEM-guidance or SOC. The primary outcome was the difference in blood products (fresh frozen plasma (FFP) or platelets) transfused between the groups. The secondary outcome was procedure-related bleeding or complications within 7 days of the procedure. The trial protocol is registered at clinicaltrails.gov; NCT05698134. Results: From August 2021 to January 2023, a total of 40 patients were recruited (ROTEM (n = 20) and SOC (n = 20)). The trial was terminated earlier during interim analyses due to compelling benefit in the ROTEM group after a scheduled interim analysis. The ROTEM group required substantially less blood transfusion than the SOC group (40% [8/20] vs 100% [20/20], P < 0.001). The benefit was consistent across all types of blood product, including fresh frozen plasma (<0.001) and pooled platelets (P = 0.046). No patients experienced clinically significant bleeding events. Transfusion-associated adverse events occurred in one patient (5%) in the SOC group (allergic reaction) and none in the ROTEM group (P = NS). The mortality in both groups at 30 and 90 days was similar. Conclusions: Viscoelastic tests like ROTEM provide global assessment of hemostasis in patients with cirrhosis. Institution of ROTEM based transfusion strategy significantly reduces the need for blood product transfusion in patients with cirrhosis undergoing elective procedure without any increased risk of bleeding events. Clinical trial number: NCT05698134.

2.
Artículo en Chino | MEDLINE | ID: mdl-39394703

RESUMEN

Objective: To investigate the molecular mechanism of autophagy and apoptosis induced by ultrafine carbon black in human bronchial epithelial cells (BEAS-2B cells), and to study the intervention effect and mechanism of N-acetylcysteine (NAC) on ultrafine carbon black-induced oxidative damage in BEAS-2B cells. Methods: In March 2023, BEAS-2B cells were used as research object, an in vitro airway model exposed to ultrafine carbon black was constructed. A control group and three carbon black exposure groups (50, 100, 200 µg/ml) were set up, and the cells were treated with corresponding concentrations of ultrafine carbon black for 24 hours. In addition, the experiment was divided into control group, NAC+ control group, 100 µg/ml carbon black exposure group and NAC+ exposure group. The corresponding groups were treated with 2 mmol/L NAC for 1 h and 100 µg/ml ultrafine carbon black for 24 h, respectively. Cell viability was measured by CCK-8 assay. Intracellular reactive oxygen species (ROS) level was detected by chemical fluorescence method. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), as well as the content of malondialdehyde (MDA) were detected by colorimetry. The mRNA and protein expressions of autophagy-related genes[Atg5, Atg7, Beclin1, microtubule-associated protein light chain 3B (LC3B), p62 and lysosome-associated membrane protein 2 (LAMP2) ] and apoptosis-related genes [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase3, Caspase9 and poly (ADP-ribose) polymerase 1 (PARP1) ] were determined by fluorescence quantitative PCR and Western blot. Cell apoptosis was determined by flow cytometry. Results: Compared with the control group, the relative survival rates of BEAS-2B cells in 50, 100, 200 µg/ml carbon black exposure groups were significantly decreased, the levels of ROS and MDA were significantly increased, and the activities of SOD, GSH-Px and CAT were significantly decreased (P<0.05). The relative survival rate, ROS and MDA levels, SOD, GSH-Px and CAT activities were significantly correlated with the exposure dose of ultrafine carbon black (r(s)=-0.755, 0.826, 0.934, -0.810, -0.880, -0.840, P<0.05). Compared with the control group, the relative expression levels of Atg5, Atg7, Beclin1, LC3B, p62, LAMP2, Bax, Caspase3, Caspase9, PARP1 mRNA and Atg5, Atg7, Beclin1, LC3BⅡ, p62, LAMP2, Bax, cleaved Caspase3 (C-Caspase3), cleaved Caspase9 (C-Caspase9), cleaved PARP1 (C-PARP1) protein and the ratio of LC3BⅡ/LC3BⅠ in 50, 100 and 200 µg/ml carbon black exposure groups were significantly increased, while the relative expression levels of Bcl-2 mRNA and protein were significantly decreased (P<0.05). The changes of the above indexes were significantly correlated with the exposure dose of carbon black (r(s)=0.892, 0.879, 0.944, 0.892, 0.828, 0.880, 0.814, 0.794, 0.931, 0.918, 0.813, 0.866, 0.774, 0.695, 0.918, 0.761, 0.794, 0.944, 0.833, 0.866, 0.905, -0.886, -0.748, P<0.05). Compared with 100 µg/ml carbon black exposure group, the relative survival rate, the activities of SOD, GSH-Px and CAT in NAC+exposure group were significantly increased, while the levels of ROS and MDA were significantly decreased, and the relative expression levels of LC3B, p62 and Caspase3 mRNA and protein as well as the ratio of LC3BⅡ/LC3BⅠ were significantly decreased, and the differences were statistically significant (P<0.05). Compared with the control group, the apoptosis rates of BEAS-2B cells in 50, 100, 200 µg/ml carbon black exposure groups were significantly increased (P<0.05), and there was a significant positive correlation between ultrafine carbon black exposure dose and cell apoptosis rate (r(s)=0.944, P<0.05). While compared with 100 µg/ml carbon black exposure group, the apoptosis rate of NAC+exposure group was significantly decreased, and the difference was statistically significant (P<0.05) . Conclusion: Cell autophagy and apoptosis may be important pathophysiological mechanisms of ultrafine carbon black-induced oxidative damage in BEAS-2B cells. NAC can alleviate the occurrence of BEAS-2B cell damage caused by ultrafine carbon black by regulating oxidative stress and the cascading autophagy and apoptosis pathways.


Asunto(s)
Acetilcisteína , Apoptosis , Autofagia , Bronquios , Células Epiteliales , Estrés Oxidativo , Hollín , Humanos , Acetilcisteína/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Bronquios/citología , Hollín/toxicidad , Estrés Oxidativo/efectos de los fármacos , Línea Celular , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Malondialdehído/metabolismo , Catalasa/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Proteína X Asociada a bcl-2/genética , Glutatión Peroxidasa/metabolismo , Supervivencia Celular/efectos de los fármacos
3.
Structure ; 2024 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-39423807

RESUMEN

The transcription factor BCL11A is a critical regulator of the switch from fetal hemoglobin (HbF: α2γ2) to adult hemoglobin (HbA: α2ß2) during development. BCL11A binds at a cognate recognition site (TGACCA) in the γ-globin gene promoter and represses its expression. DNA-binding is mediated by a triple zinc finger domain, designated ZnF456. Here, we report comprehensive investigation of ZnF456, leveraging X-ray crystallography and NMR to determine the structures in both the presence and absence of DNA. We delve into the dynamics and mode of interaction with DNA. Moreover, we discovered that the last zinc finger of BCL11A (ZnF6) plays a different role compared to ZnF4 and 5, providing a positive entropic contribution to DNA binding and γ-globin gene repression. Comprehending the DNA binding mechanism of BCL11A opens avenues for the strategic, structure-based design of novel therapeutics targeting sickle cell disease and ß-thalassemia.

4.
Zhonghua Nei Ke Za Zhi ; 63(10): 922-926, 2024 Oct 01.
Artículo en Chino | MEDLINE | ID: mdl-39375111
5.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 42(10): 752-756, 2024 Oct 20.
Artículo en Chino | MEDLINE | ID: mdl-39472138

RESUMEN

Objective: To evaluate the risk of major chemical exposure positions in copper and nickel smelting enterprises, and provide a basis for risk assessment and prevention control measures. Methods: From September to October 2023, two copper nickel ore smelting enterprises in Xinjiang Uygur Autonomous Region were selected as the research objects. Relevant information on chemicals was collected through occupational hazard field investigations. Qualitative analysis and exposure index methods were used in GBZ/T 298-2017 "Technical Guidelines for Occupational Health Risk Assessment of Chemical Hazardous Factors in the Workplace" to conduct risk assessments on the main chemical exposure positions. The qualitative risk assessment results were checked for consistency using the Weighted Kappa coefficient. Results: The positions with high risk of exposure to hazardous chemicals in copper nickel smelting enterprises are saponification positions exposed to hydrochloric acid in refining processes, black nickel positions exposed to sodium hydroxide, and tail suction positions. The consistency between the two occupational health risk assessment results is poor (Kappa=0.14) . Conclusion: The amount of major hazardous chemicals in copper-nickel smelting enterprises is large, and the occupational health risks caused by exposure are complex and diverse, so the effects of chronic occupational health should be strengthened.


Asunto(s)
Cobre , Sustancias Peligrosas , Níquel , Exposición Profesional , Salud Laboral , Níquel/análisis , Medición de Riesgo , Exposición Profesional/análisis , Humanos , Sustancias Peligrosas/análisis , Lugar de Trabajo
6.
Phys Rev Lett ; 133(15): 152502, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39454169

RESUMEN

We extend the QCD Parton Model analysis using a factorized nuclear structure model incorporating individual nucleons and pairs of correlated nucleons. Our analysis of high-energy data from lepton deep-inelastic scattering, Drell-Yan, and W and Z boson production simultaneously extracts the universal effective distribution of quarks and gluons inside correlated nucleon pairs, and their nucleus-specific fractions. Such successful extraction of these universal distributions marks a significant advance in our understanding of nuclear structure properties connecting nucleon- and parton-level quantities.

7.
Zhonghua Xin Xue Guan Bing Za Zhi ; 52(9): 1058-1064, 2024 Sep 24.
Artículo en Chino | MEDLINE | ID: mdl-39289996

RESUMEN

Objective: To explore the relationship between the hypertensive snowbirds' length of migratory stay and their blood pressure control and blood pressure levels. Methods: This study was a cross-sectional study. A population of snowbirds with hypertension was recruited between October and November 2022, and a structured questionnaire was used to collect their self-measured blood pressure and length of stay in Hainan Province. The blood pressure control status is determined based on self-measured blood pressure. According to the self-measured blood pressure to determine whether the blood pressure was well controlled. The associations between snowbirds' length of stay and their blood pressure control as well as their self-measured blood pressure were analyzed using restricted cubic splines. Results: A total of 362 research subjects were included, 169(46.7%) of whom were male, and their age was (69.7±7.0) years old. The participants' self-measured systolic blood pressure and diastolic blood pressure were (129.1±16.2) mmHg (1 mmHg=0.133 kPa) and (78.9±10.1) mmHg, respectively. Overall, 174 (48.1%) participants attained adequate blood pressure control. The median length of stay in Wuzhishan City was 7(6, 7) months. There was an inverted U-shaped association between snowbirds' length of stay and blood pressure control (overall: P=0.023; nonlinearity: P=0.014), where participants with a length of stay of 7 months had the highest rate of blood pressure control. There is a U-shaped curve relationship between length of stay and systolic blood pressure (overall: P=0.001; nonlinearity: P=0.033), and a linear negative correlation with diastolic blood pressure (ß=-1.19, P=0.003). Conclusions: Compared with hypertensive snowbirds with too long or too short lengths of stay, snowbirds who stayed in Wuzhishan City for seven months have better blood pressure control, and systolic blood pressure is also lower.


Asunto(s)
Presión Sanguínea , Hipertensión , Masculino , Hipertensión/epidemiología , Femenino , Estudios Transversales , Animales , Anciano , Humanos , Persona de Mediana Edad , Encuestas y Cuestionarios , Aves , Migración Animal , China/epidemiología
8.
Periodontol 2000 ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39318055

RESUMEN

Surgical removal of impacted mandibular third molars is often followed by postoperative sequelae like pain, swelling, trismus, etc. This systematic review explored the benefits of applying different autologous platelet concentrates (APCs) in the extraction socket of third molars. For this systematic review, PubMed, EMBASE, Web of Science, and Scopus have been utilized, initially yielding 544 papers. The search was narrowed to randomized controlled trials (RCTs, n = 59) published before 2024, all comparing the outcome of applying APCs in the extraction socket of surgically removed impacted mandibular third molars with unassisted healing (blood clot). Most RCTs primarily assessed the impact of APCs on postoperative sequelae. Some RCTs looked at soft- and hard-tissue healing. Eleven studies used PRP, three PRGF, and 45 L-PRF. A detailed analysis revealed a large heterogeneity between studies rendering a meta-analysis impossible. Moreover, the risk of bias was considered high. In the majority of RCTs, the application of an APC resulted in statistically significant reductions of postoperative sequelae (lower pain intensity, lower consumption of analgesics, less postoperative edema, and a lower incidence of trismus and alveolar osteitis), as well as a faster soft tissue healing, and qualitatively and quantitatively better bone healing. A minority of studies reported significant differences in periodontal parameters distally from the second molar.

9.
Sci Adv ; 10(39): eado1219, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39331711

RESUMEN

The Pacific large low-shear-velocity province (LLSVP), as revealed by cluster analysis of global tomographic models, hosts multiple internal anomalies, including a notable gap (~20° wide) between the central and eastern Pacific. The cause of the structural gap remains unconstrained. Directly above this structural gap, we identify an anomalously thick mantle transition zone east of the East Pacific Rise, the fastest-spreading ocean ridge in the world, using a dense set of SS precursors. The area of the thickened transition zone exhibits faster-than-average velocities according to recent tomographic images, suggesting perturbed postolivine phase boundaries shifting in response to lowered temperatures. We attribute this observation to episodes of Mesozoic-aged (250 to 120 million years ago) intraoceanic subduction beneath the present-day Nazca Plate. The eastern portion of the Pacific LLSVP was separated by downwelling because of this ancient oceanic slab. Our discovery provides a unique perspective on linking deep Earth structures with surface subduction.

10.
Sci Adv ; 10(36): eado0403, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39231223

RESUMEN

The current standard method for amino acid signal identification in protein NMR spectra is sequential assignment using triple-resonance experiments. Good software and elaborate heuristics exist, but the process remains laboriously manual. Machine learning does help, but its training databases need millions of samples that cover all relevant physics and every kind of instrumental artifact. In this communication, we offer a solution to this problem. We propose polyadic decompositions to store millions of simulated three-dimensional NMR spectra, on-the-fly generation of artifacts during training, a probabilistic way to incorporate prior and posterior information, and integration with the industry standard CcpNmr software framework. The resulting neural nets take [1H,13C] slices of mixed pyruvate-labeled HNCA spectra (different CA signal shapes for different residue types) and return an amino acid probability table. In combination with primary sequence information, backbones of common proteins (GB1, MBP, and INMT) are rapidly assigned from just the HNCA spectrum.


Asunto(s)
Proteínas , Proteínas/química , Resonancia Magnética Nuclear Biomolecular/métodos , Programas Informáticos , Aminoácidos/química , Algoritmos , Isótopos/química , Aprendizaje Automático
11.
J Hypertens ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39248145

RESUMEN

BACKGROUND: A recent call-to-action highlighted that Australia is lagging behind high-income countries regarding hypertension control rates. METHODS: We performed a systematic literature search of reports on prevalence, awareness, treatment and control rates since 2010. We also undertook an individual participant data meta-analysis of six population-based studies in the general population from 1980 to 2018 to understand the size of the problem and trajectories over time. RESULTS: The aggregated data showed that after 2010, hypertension prevalence was 31% ]95% confidence interval (CI) 27-34%], and awareness, treatment, and control rates among people with hypertension were 56% (41-71%), 54% (46-62%) and 34% (22-47%), respectively. Since 1980, these figures have shown slight improvement. However, we noted a low availability of quality nationwide randomized databases for Australia. CONCLUSIONS: We require critical action to improve the prevention, detection and treatment of hypertension, and highlight the need for large-scale investment in tracking population health in order to produce vital health statistics for the nation.

12.
Public Health ; 236: 184-192, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39299085

RESUMEN

OBJECTIVES: To synthesize eye-tracking-based evidence on consumers' visual attention devoted to alcohol warning labels (AWLs) on alcohol packaging. STUDY DESIGN: A systematic review was conducted and reported in accordance with the PRISMA guidelines. METHODS: Two rounds of a literature search were conducted to identify relevant peer-reviewed articles and unpublished grey literature. While the first round (July 3 to August 21, 2023) was based on three electronic databases (PubMed, Web of Science, and PsycINFO), the second round (May 20 to 28, 2024) followed a multiple-step protocol that systematically searched the grey literature. Five criteria were applied to screen eligible articles. Using established quality control tools, the identified articles were assessed for overall quality and then for quality specific to the eye-tracking method. RESULTS: Six published peer-reviewed articles were thus included in the current review along with one unpublished research paper from a doctoral thesis. This review paper summarizes earlier findings in terms of bottom-up (i.e., AWL design-related) factors such as size, color, surrounding border, and pictorial elements, and top-down (i.e., goal-driven) factors such as motivation to change drinking behavior and self-affirmation. The review found that people tend to pay very little attention to AWLs displayed on alcohol packaging, although there is mixed evidence as to the effectiveness of specific factors. CONCLUSIONS: Further investigations using eye-tracking are needed to collect additional evidence on attention devoted to AWLs. Meanwhile, we put forward implications for policymakers and future avenues for research based on our review of the existing literature.

13.
Malar J ; 23(1): 280, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39285410

RESUMEN

BACKGROUND: Intensive deployment of insecticide based malaria vector control tools resulted in the rapid evolution of phenotypes resistant to these chemicals. Understanding this process at the genomic level is important for the deployment of successful vector control interventions. Therefore, longitudinal sampling followed by whole genome sequencing (WGS) is necessary to understand how these evolutionary processes evolve over time. This study investigated the change in genetic structure and the evolution of the insecticide resistance variants in natural populations of Anopheles gambiae over time and space from 2012 to 2017 in Burkina Faso. METHODS: New genomic data have been generated from An. gambiae mosquitoes collected from three villages in the western part of Burkina Faso between 2012 and 2017. The samples were whole-genome sequenced and the data used in the An. gambiae 1000 genomes (Ag1000G) project as part of the Vector Observatory. Genomic data were analysed using the analysis pipeline previously designed by the Ag1000G project. RESULTS: The results showed similar and consistent nucleotide diversity and negative Tajima's D between An. gambiae sensu stricto (s.s.) and Anopheles coluzzii. Principal component analysis (PCA) and the fixation index (FST) showed a clear genetic structure in the An. gambiae sensu lato (s.l.) species. Genome-wide FST and H12 scans identified genomic regions under divergent selection that may have implications in the adaptation to ecological changes. Novel voltage-gated sodium channel pyrethroid resistance target-site alleles (V402L, I1527T) were identified at increasing frequencies alongside the established alleles (Vgsc-L995F, Vgsc-L995S and N1570Y) within the An. gambiae s.l. POPULATIONS: Organophosphate metabolic resistance markers were also identified, at increasing frequencies, within the An. gambiae s.s. populations from 2012 to 2017, including the SNP Ace1-G280S and its associated duplication. Variants simultaneously identified in the same vector populations raise concerns about the long-term efficacy of new generation bed nets and the recently organophosphate pirimiphos-methyl indoor residual spraying in Burkina Faso. CONCLUSION: These findings highlighted the benefit of genomic surveillance of malaria vectors for the detection of new insecticide resistance variants, the monitoring of the existing resistance variants, and also to get insights into the evolutionary processes driving insecticide resistance.


Asunto(s)
Anopheles , Resistencia a los Insecticidas , Mosquitos Vectores , Secuenciación Completa del Genoma , Resistencia a los Insecticidas/genética , Anopheles/genética , Anopheles/efectos de los fármacos , Animales , Burkina Faso , Mosquitos Vectores/genética , Mosquitos Vectores/efectos de los fármacos , Estudios Longitudinales , Evolución Molecular , Insecticidas/farmacología , Malaria/transmisión
14.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(9): 863-868, 2024 Sep 12.
Artículo en Chino | MEDLINE | ID: mdl-39266488

RESUMEN

Patients with SARS-CoV-2 infection often exhibit significant changes in T cells, particularly a reduction in CD4+T and CD8+T cells in peripheral blood, which has become a key feature of severe respiratory infection. These immune changes in T lymphocytes are closely associated with disease progression, but the specific mechanisms remain unclear and warrant further investigation. This paper reviewed the changes in the number and function of T cells in respiratory viral infections, with a focus on SARS-CoV-2, and summarized related therapeutic explorations. We believe that improving and enhancing the number and function of T lymphocytes in infected hosts is a promising strategy for the treatment of respiratory viral infections, although more systematic and in-depth scientific research is still needed.


Asunto(s)
Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/inmunología , SARS-CoV-2/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T/inmunología
15.
Zhonghua Xue Ye Xue Za Zhi ; 45(7): 689-693, 2024 Jul 14.
Artículo en Chino | MEDLINE | ID: mdl-39231775

RESUMEN

This study reports on three patients with Shwachman-Diamond syndrome (SDS) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the First Affiliated Hospital of Zhejiang University School of Medicine. Based on relevant literature, the clinical manifestations and genetic mutation characteristics of SDS were summarized, and the efficacy and timing of allo HSCT for such patients were explored. Three SDS patients were all male, with transplant ages of 32, 33, and 32 years old, respectively. All three patients were diagnosed in childhood. Case 1 presented with anemia as the initial clinical manifestation, which gradually progressed to a decrease in whole blood cells; Case 2 and 3 both present with a decrease in whole blood cells as the initial clinical manifestation. Case 1 and 3 have intellectual disabilities, while case 3 presents with pancreatic steatosis and chronic pancreatitis. All three patients have short stature. Three patients all detected heterozygous mutations in the SBDS: c.258+2T>C splice site. The family members of the three patients have no clinical manifestations of SDS. All three patients were treated with a reduced dose pre-treatment regimen (Fludarabine+Busulfan+Me-CCNU+Rabbit Anti-human Thymocyte Globulin). Case 1 and case 2 underwent haploid hematopoietic stem cell transplantation, while case 3 underwent unrelated donor hematopoietic stem cell transplantation. Case 1 was diagnosed with myelodysplastic syndrome transforming into acute myeloid leukemia before transplantation, but experienced early recurrence and death after transplantation; Case 2 is secondary implantation failure, dependent on platelet transfusion; Case 3 was removed from medication maintenance treatment after transplantation, and blood routine monitoring was normal.


Asunto(s)
Insuficiencia Pancreática Exocrina , Trasplante de Células Madre Hematopoyéticas , Lipomatosis , Síndrome de Shwachman-Diamond , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Masculino , Adulto , Insuficiencia Pancreática Exocrina/terapia , Trasplante Homólogo , Enfermedades de la Médula Ósea/terapia , Mutación
16.
Nature ; 633(8028): 174-181, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39198639

RESUMEN

Sterile inflammation after myocardial infarction is classically credited to myeloid cells interacting with dead cell debris in the infarct zone1,2. Here we show that cardiomyocytes are the dominant initiators of a previously undescribed type I interferon response in the infarct borderzone. Using spatial transcriptomics analysis in mice and humans, we find that myocardial infarction induces colonies of interferon-induced cells (IFNICs) expressing interferon-stimulated genes decorating the borderzone, where cardiomyocytes experience mechanical stress, nuclear rupture and escape of chromosomal DNA. Cardiomyocyte-selective deletion of Irf3 abrogated IFNIC colonies, whereas mice lacking Irf3 in fibroblasts, macrophages, neutrophils or endothelial cells, Ccr2-deficient mice or plasmacytoid-dendritic-cell-depleted mice did not. Interferons blunted the protective matricellular programs and contractile function of borderzone fibroblasts, and increased vulnerability to pathological remodelling. In mice that died after myocardial infarction, IFNIC colonies were immediately adjacent to sites of ventricular rupture, while mice lacking IFNICs were protected from rupture and exhibited improved survival3. Together, these results reveal a pathological borderzone niche characterized by a cardiomyocyte-initiated innate immune response. We suggest that selective inhibition of IRF3 activation in non-immune cells could limit ischaemic cardiomyopathy while avoiding broad immunosuppression.


Asunto(s)
Interferón Tipo I , Infarto del Miocardio , Animales , Femenino , Humanos , Masculino , Ratones , Células Dendríticas/inmunología , Células Endoteliales/metabolismo , Fibroblastos/metabolismo , Perfilación de la Expresión Génica , Inmunidad Innata , Factor 3 Regulador del Interferón/antagonistas & inhibidores , Factor 3 Regulador del Interferón/deficiencia , Factor 3 Regulador del Interferón/metabolismo , Interferón Tipo I/metabolismo , Interferón Tipo I/inmunología , Macrófagos/metabolismo , Macrófagos/inmunología , Ratones Endogámicos C57BL , Infarto del Miocardio/inmunología , Infarto del Miocardio/patología , Infarto del Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Neutrófilos/metabolismo , Receptores CCR2/metabolismo , Receptores CCR2/deficiencia , Receptores CCR2/genética
17.
J Cancer Res Ther ; 20(4): 1130-1140, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39206974

RESUMEN

ABSTRACT: Intestinal microecology (IM) is the largest and most important microecological system of the human body. Furthermore, it is the key factor for activating and maintaining the physiological functions of the intestine. Numerous studies have investigated the effects of the gut microbiota on the different tissues and organs of the human body as well as their association with various diseases, and the findings are gradually being translated into clinical practice. The gut microbiota affects the occurrence, progression, treatment response, and toxic side effects of tumors. The deepening of research related to IM and tumors has opened a new chapter in IM research driven by methods and technologies such as second-generation sequencing and bioinformatics. The IM maintains the function of the host immune system and plays a pivotal role in tumor-control drug therapy. Increasing evidence has proven that the efficacy of tumor-control drugs largely depends on the IM balance, and strategies based on the IM technology show promising application prospects in the diagnosis and treatment of tumor. The Tumor and Microecology Professional Committee of the Chinese Anti-cancer Association gathered relevant experts to discuss and propose the "Chinese guidelines for integrated diagnosis and treatment of IM technologies in tumor application (2024 Edition)," which was established based on the research progress of the application of the IM technology in tumor to provide a basis for the standardization of the diagnosis and treatment of the IM technology in the tumor.


Asunto(s)
Microbioma Gastrointestinal , Neoplasias , Humanos , China , Microbioma Gastrointestinal/efectos de los fármacos , Neoplasias/diagnóstico , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/patología
18.
Public Health ; 235: 152-159, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39137656

RESUMEN

OBJECTIVE: The objective of this study was to investigate the effects of self-management education integrated with text-message support (SME-TMS) on glycaemic control in individuals with type 2 diabetes. STUDY DESIGN: a randomized, controlled trial. METHODS: Patients from two communities were randomized into the intervention group (n = 53) or the control group (n = 52). The six-month intervention included the culturally tailored diabetes education and text-messaging support for behaviour changes. The control group received treatment as usual. The primary outcome was reductions in HbA1c and fasting blood glucose at six-month non-intervention follow-up. Secondary outcomes were reductions in body weight, body mass index (BMI), blood pressure, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, physical activity, and health beliefs. RESULTS: The intervention led to substantially increase days of weekly physical activity (42% vs. 0%, P < 0.001) and health beliefs (coefficient = 7.0, 95% confidence interval [CI]: 4.4 to 9.6, P < 0.001). However, no greater reduction was found in HbA1c at six months after the intervention, compared with the control group (0.13%, 95% CI: -0.20 to 0.46, P = 0.443). The reductions of blood pressure, TC, and LDL-C were greater in the control group than in the intervention group (all P < 0.050). Within the intervention group, participants had significant reduction in BMI, whereas the control group had greater reductions in TC and LDL-C (all P < 0.050). CONCLUSIONS: The SME-TMS intervention led to a greater increase in the weekly physical activity and health belief score in the older patients at 6-month follow-up than with the usual care. Further research is needed to ascertain how these benefits could be translated into favorable medium-and long-term glycaemic control. TRAIL REGISTRATION NUMBER: This study was registered on Chinese Clinical Trials Registry (ChiCTR2300075112).


Asunto(s)
Diabetes Mellitus Tipo 2 , Envío de Mensajes de Texto , Humanos , Diabetes Mellitus Tipo 2/terapia , Masculino , Femenino , Anciano , Persona de Mediana Edad , Hemoglobina Glucada/análisis , Educación del Paciente como Asunto/métodos , Ejercicio Físico , Estilo de Vida , Glucemia/análisis , Automanejo/métodos , Índice de Masa Corporal
20.
Zhonghua Yi Xue Za Zhi ; 104(27): 2513-2520, 2024 Jul 16.
Artículo en Chino | MEDLINE | ID: mdl-38978375

RESUMEN

Objective: To explore the efficacy of venetoclax-based induction regimen for children with newly diagnosed acute myeloid leukemia (AML). Methods: Children with newly diagnosed AML in Beijing Children's Hospital Affiliated to Capital Medical University and Baoding Hospital Affliliated to Capital Medical University from November 2019 and December 2023 were prospectively included. The patients were divided into DAH group (daunorubicin, cytarabine and homoharringtonine) and VAH group (venetoclax, cytarabine and homoharringtonine) according to induction regimen. The clinical data of the children were collected, the clinical characteristics and induced remission rate between the two groups were compared, and multivariate logistic regression was used to analyze the related factors affecting the induced remission rate. Results: A total of 135 patients were enrolled, including 96 cases in the DAH group (54 males and 42 females), aged [M (Q1, Q3)] 6.4 (3.9, 11.6) years and 39 cases in the VAH group (26 males and 13 females), aged 8.0 (6.2, 13.2) years. Among patients initially diagnosed with low-medium risk AML, the morphologic complete remission rates were 94.7% (18/19) in the VAH group and 84.4% (38/45) in the DAH group, respectively, and the negativity conversion rates of minirnal residual disease (MRD) were 57.9% (11/19) and 46.7% (21/45), respectively, with no statistically difference (all P>0.05). Among patients initially diagnoised with high-risk AML, the morphologic complete remission rates in the VAH group was higher than that in the DAH group [95.0% (19/20) vs 70.6% (36/51), P=0.027], and negativity conversion rates of MRD were 45.0% (9/20) and 33.3% (17/51), respectively, with no statistically difference (P=0.359). The induction regimen (venetoclax, cytarabine and homoharringtonin) was beneficial to morphological remission (OR=0.126, 95%CI: 0.025-0.629). FLT3 mutation was not conducive to morphological remission (OR=5.832, 95%CI: 1.778-19.124) and negative MRD (OR=4.166, 95%CI: 1.396-12.433). Conclusion: Venetoclax-based induction regimen is more effective than traditional chemotherapy regimen for newly diagnosed pediatric AML.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Compuestos Bicíclicos Heterocíclicos con Puentes , Citarabina , Leucemia Mieloide Aguda , Sulfonamidas , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Niño , Masculino , Femenino , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Citarabina/administración & dosificación , Citarabina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Preescolar , Inducción de Remisión , Adolescente , Daunorrubicina/administración & dosificación , Daunorrubicina/uso terapéutico , Quimioterapia de Inducción , Homoharringtonina/administración & dosificación , Homoharringtonina/uso terapéutico , Estudios Prospectivos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...