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1.
Sci Total Environ ; 932: 173056, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38723958

RESUMEN

We investigated the photocatalytic property of etched iron­aluminum layered double hydroxide (LDH) composites using urea-modified biochar (N-BC) carrier to degrade para-aminobenzoic acid (PABA), a refractory organic pollutant. The prepared FeAl-LDH@FeSx-N-BC composite exhibited excellent photocatalytic performance, attributed to the enhanced photogenerated charge-carrier separation by the etched LDH and the improved comparative surface areas by the doped N-BC. The composite photocatalytically degraded 96 % of PABA. The performance was affected by solute concentration, pH and photocatalyst dose. Adding p-benzoquinone and EDTA-2Na significantly decreased the degradation rate, suggesting that superoxide radicals and holes were co-involved in PABA degradation. The excellent PABA removal efficiency was consistent for three consecutive runs. The samples' reactive oxygen species was confirmed, as electron paramagnetic reverberation explained the photodegradation mechanism. Under xenon lamp irradiation, two PABA photocatalytic degradation pathways were proposed using Liquid Chromatograph Mass Spectrometer (LCMS) and density functional theory. As expected, FeAl-LDH@FeSx-N-BC showed excellent photocatalytic performance, expanding a new direction and possibility for future photocatalytic treatment of water pollutants.

2.
Sci Rep ; 14(1): 10621, 2024 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-38729969

RESUMEN

Asymptomatic Leucine-Rich Repeat Kinase 2 Gene (LRRK2) carriers are at risk for developing Parkinson's disease (PD). We studied presymptomatic substantia nigra pars compacta (SNc) regional neurodegeneration in asymptomatic LRRK2 carriers compared to idiopathic PD patients using neuromelanin-sensitive MRI technique (NM-MRI). Fifteen asymptomatic LRRK2 carriers, 22 idiopathic PD patients, and 30 healthy controls (HCs) were scanned using NM-MRI. We computed volume and contrast-to-noise ratio (CNR) derived from the whole SNc and the sensorimotor, associative, and limbic SNc regions. An analysis of covariance was performed to explore the differences of whole and regional NM-MRI values among the groups while controlling the effect of age and sex. In whole SNc, LRRK2 had significantly lower CNR than HCs but non-significantly higher volume and CNR than PD patients, and PD patients significantly lower volume and CNR compared to HCs. Inside SNc regions, there were significant group effects for CNR in all regions and for volumes in the associative region, with a trend in the sensorimotor region but no significant changes in the limbic region. PD had reduced volume and CNR in all regions compared to HCs. Asymptomatic LRRK2 carriers showed globally decreased SNc volume and CNR suggesting early nigral neurodegeneration in these subjects at risk of developing PD.


Asunto(s)
Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Imagen por Resonancia Magnética , Melaninas , Enfermedad de Parkinson , Sustancia Negra , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/genética , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Melaninas/metabolismo , Imagen por Resonancia Magnética/métodos , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/metabolismo , Sustancia Negra/diagnóstico por imagen , Sustancia Negra/patología , Sustancia Negra/metabolismo , Anciano , Heterocigoto , Adulto , Estudios de Casos y Controles
3.
Front Cell Infect Microbiol ; 14: 1371916, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38716199

RESUMEN

Porcine epidemic diarrhea virus (PEDV) has become a challenging problem in pig industry worldwide, causing significant profit losses. Lactobacillus rhamnosus GG (LGG) has been regarded as a safe probiotic strain and has been shown to exert protective effects on the intestinal dysfunction caused by PEDV. This study evaluated the effect of LGG on the gut health of lactating piglets challenged with PEDV. Fifteen piglets at 7 days of age were equally assigned into 3 groups (5 piglets per group): 1) control group (basal diet); 2) PEDV group: (basal diet + PEDV challenged); 3) LGG + PEDV group (basal diet + 3×109 CFU/pig/day LGG + PEDV). The trial lasted 11 days including 3 days of adaptation. The treatment with LGG was from D4 to D10. PEDV challenge was carried out on D8. PEDV infection disrupted the cell structure, undermined the integrity of the intestinal tract, and induced oxidative stress, and intestinal damage of piglets. Supplementation of LGG improved intestinal morphology, enhanced intestinal antioxidant capacity, and alleviated jejunal mucosal inflammation and lipid metabolism disorders in PEDV-infected piglets, which may be regulated by LGG by altering the expression of TNF signaling pathway, PPAR signaling pathway, and fat digestion and absorption pathway.


Asunto(s)
Infecciones por Coronavirus , Suplementos Dietéticos , Lacticaseibacillus rhamnosus , Virus de la Diarrea Epidémica Porcina , Probióticos , Enfermedades de los Porcinos , Animales , Porcinos , Probióticos/administración & dosificación , Enfermedades de los Porcinos/prevención & control , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/terapia , Estrés Oxidativo , Intestinos/patología , Polvos , Mucosa Intestinal/patología
4.
Int J Surg Case Rep ; 119: 109709, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38718492

RESUMEN

INTRODUCTION: Pericoronitis of wisdom teeth along the jaw diffusion may be a rare diffusion pathway, which can cause osteomyelitis and maxillofacial space infection serious complications. PRESENTATION OF CASE: A 62-years-old male patient presented with swelling and discomfort of the right cheek for more than 1 year. The patient was previously healthy and denied various systemic medical histories. The patient's face was asymmetric, the right cheek was swollen, and the depressed edema was seen on the surface of the masseter area of the right parotid gland. Based on the preoperative cone-beam computed tomography (CBCT) imaging results, the initial diagnosis was: centralized osteomyelitis of the jaws. The surgical plan was minimally invasive extraction 48 and localized debridement of the lesion area. After three months of follow-up, the patient's symptoms were significantly improved without recurrence. DISCUSSION: Pericoronitis of wisdom teeth along the jaw diffusion is a rare diffusion pathway, which can lead to secondary jaw osteomyelitis, the treatment of which consists of lesion debridement, dead bone curettage and antibiotic therapy. CONCLUSION: Through literature review and summary of the diagnosis and treatment process of this case, such cases should be diagnosed as early as possible and conservative treatment should be actively used to avoid the occurrence of complications. In addition, the special diffusion pathway of this case may provide a new theoretical basis for the source of infection of central jaw osteomyelitis.

5.
ACS Catal ; 14(9): 7157-7165, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38721382

RESUMEN

With heterogeneous catalysts, chemical promotion takes place at their surfaces. Even in the case of single-atom alloys, where small quantities of a reactive metal are dispersed within the main host, it is assumed that both elements are exposed and available to bond with the reactants. Here, we show, on the basis of in situ X-ray absorption spectroscopy data, that in alloy catalysts made from Pt highly diluted in Cu the Pt atoms are located at the inner interface between the metal nanoparticles and the silica support instead. Kinetic experiments indicated that these catalysts still display better selectivity for the hydrogenation of unsaturated aldehydes to unsaturated alcohols than the pure metals. Density functional theory calculations corroborated the stability of Pt at the metal-support interface and explained the catalytic performance as being due to a remote lowering of the activation barrier for the dissociation of H2 at Cu sites by the internal Pt atoms.

6.
Diagn Microbiol Infect Dis ; 109(3): 116278, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38723451

RESUMEN

The aim of this study was to evaluate the influence factors of metagenomic next-generation sequencing (mNGS) negative results in the diagnosed patients with spinal infection. mNGS test was applied in a cohort of 114 patients with suspected spinal infection, among which 56 patients had a final diagnosis of spinal infection. mNGS achieved a sensitivity of 75.0% (95% CI, 61.6% to 85.6%) and a specificity of 84.5% (95% CI, 72.6% to 92.7%), using histopathology and culture results as reference. Diagnosed patients with a negative culture result had lower white blood cell account, percentage of neutrophilic granulocyte, C-reactive protein (all P<0.05) and relatively higher rate of prior antimicrobial treatment history (P=0.059). However, diagnosed patients with a negative mNGS result did not have such difference with mNGS-positive patients, suggesting that mNGS was not strictly limited by the above indicators, which presented the advantages of this technique from another point of view.

7.
Sci Rep ; 14(1): 10085, 2024 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-38698166

RESUMEN

The North China Plain (NCP) is one of the three great plains in China and also serves as a vital region for grain, cotton, and oil production. Under the influence of regional hydrothermal changes, groundwater overexploitation, and seawater intrusion, the vegetation coverage is undergoing continuous alterations. However, a comprehensive assessment of impacts of precipitation, temperature, and groundwater on vegetation in marine sedimentary regions of the NCP is lacking. Heilonggang Basin (HB) is located in the low-lying plain area in the east of NCP, which is part of the NCP. In this study, the HB was chosen as a typical area of interest. We collected a series of data, including the Normalized Difference Vegetation Index (NDVI), precipitation, temperature, groundwater depth, and Total Dissolved Solids (TDS) from 2001 to 2020. Then the spatiotemporal variation in vegetation was analyzed, and the underlying driving mechanisms of vegetation variation were explored in this paper. The results show that NDVI experiences a rapid increase from 2001 to 2004, followed by stable fluctuations from 2004 to 2020. The vegetation in the HB has achieved an overall improvement in the past two decades, with 76% showing improvement, mainly in the central and eastern areas, and 24% exhibiting deterioration in other areas. From 2001 to 2020, NDVI correlates positively with precipitation, whereas its relationship with temperature fluctuates between positive and negative, and is not statistically significant. There is a threshold for the synergistic change of NDVI and groundwater depth. When the groundwater depth is lower than 3.8 m, NDVI increases sharply with groundwater depth. However, beyond this threshold, NDVI tends to stabilize and fluctuate. In the eastern coastal areas, NDVI exhibits a strong positive correlation with groundwater depth, influenced by the surface soil TDS controlled by groundwater depth. In the central regions, a strong negative correlation is observed, where NDVI is primarily impacted by soil moisture under the control of groundwater. In the west and south, a strong positive correlation exists, with NDVI primarily influenced by the intensity of groundwater exploitation. Thus, precipitation and groundwater are the primary driving forces behind the spatiotemporal variability of vegetation in the HB, while in contrast, the influence of temperature is uncertain. This study has elucidated the mechanism of vegetation response, providing a theoretical basis for mitigating adverse factors affecting vegetation growth and formulating rational water usage regulations in the NCP.


Asunto(s)
Agua Subterránea , China , Agua Subterránea/análisis , Sedimentos Geológicos/análisis , Temperatura , Análisis Espacio-Temporal , Monitoreo del Ambiente/métodos , Clima , Plantas , Ecosistema
8.
J Oral Implantol ; 50(2): 75-80, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38702870

RESUMEN

The most challenging and time-consuming step in the free gingival graft (FGG) for keratinized mucosa augmentation is the compression suture anchoring the FGG to the periosteum. This article proposed a novel "microscrew with tie-down sutures" technique to anchor the FGG to the recipient site without the traditional trans-periosteum suture. This patient's keratinized mucosa width (KMW) around the healing abutments of teeth #29 and #30 was less than 1 mm. After an apically positioned flap (AFP) was prepared, 2 microscrews were placed at the buccal plate of the alveolar ridge bone, which is the coronal margin of the AFP. Then, the sutures winded between the microscrews and the healing abutments to anchor the FGG. In conclusion, the "microscrew with tie-down sutures" technique offers a feasible and straightforward alternative for the trans-periosteum compression suture, mainly when the periosteum is fragile, thin, or injured.


Asunto(s)
Encía , Técnicas de Sutura , Humanos , Encía/cirugía , Periostio/cirugía , Femenino , Aumento de la Cresta Alveolar/métodos , Masculino
9.
Materials (Basel) ; 17(9)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38730811

RESUMEN

This paper investigates the impact of varying the part geometric complexity and 3D printing process setup on the resulting structural load bearing capacity of fiber composites. Three levels of geometric complexity are developed through 2.5D topology optimization, 3D topology optimization, and 3D topology optimization with directional material removal. The 3D topology optimization is performed with the SIMP method and accelerated by high-performance computing. The directional material removal is realized by incorporating the advection-diffusion partial differential equation-based filter to prevent interior void or undercut in certain directions. A set of 3D printing and mechanical performance tests are performed. It is interestingly found that, the printing direction affects significantly on the result performance and if subject to the uni direction, the load-bearing capacity increases from the 2.5D samples to the 3D samples with the increased complexity, but the load-bearing capacity further increases for the 3D simplified samples due to directional material removal. Hence, it is concluded that a restricted structural complexity is suitable for topology optimization of 3D-printed fiber composites, since large area cross-sections give more degrees of design freedom to the fiber path layout and also makes the inter-layer bond of the filaments firmer.

10.
Clin Res Cardiol ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740723

RESUMEN

BACKGROUND: Both the clinical and mechanistic impacts of endocan were not well elucidated especially in coronary artery disease (CAD). OBJECTIVE: This study aimed to investigate the prognostic and potential pathological role of endocan for cardiovascular (CV) events in stable CAD patients. METHODS: A total of 1,071 stable CAD patients with previous percutaneous coronary intervention (PCI) were enrolled prospectively in a nationwide Biosignature study. Another cohort of 76 CAD patients with or without PCI were enrolled for validation. Baseline biomarkers including endocan level was measured and total CV events especially hard CV events (including CV mortality, non-fatal myocardial infection and stroke) during follow-up were identified. Circulating endothelial progenitor cells (EPCs) as an in vivo biological contributor to vascular repairment from CAD patients were used for the in vitro functional study. RESULTS: After 24 months, there were 42 patients (3.92%) with hard CV events and 207 (19.3%) with total CV events in the study group. The incidence of both events was increased with the tertiles of baseline endocan level (hard events: 1.7%,3.4%, and 6.7% in 1st,2nd, and 3rd tertile respectively, p = 0.002; total events: 13.8%vs.16.2%vs.28.0%, p < 0.0001). Multivariate regression analysis revealed the independent association of endocan level with total and hard CV events. These findings were validated in another cohort with a 5-year follow-up. Furthermore, in vitro inhibition of endocan improved cell migration and tube formation capacities, and reduced cell adhesiveness of EPCs from CAD patients. CONCLUSIONS: Endocan might be a novel prognostic indicator, mechanistic mediator, and potential therapeutic target for clinical CAD.

11.
Nat Microbiol ; 9(5): 1256-1270, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38649412

RESUMEN

Epstein-Barr virus (EBV) can infect both B cells and epithelial cells (ECs), causing diseases such as mononucleosis and cancer. It enters ECs via Ephrin receptor A2 (EphA2). The function of interferon-induced transmembrane protein-1 (IFITM1) in EBV infection of ECs remains elusive. Here we report that IFITM1 inhibits EphA2-mediated EBV entry into ECs. RNA-sequencing and clinical sample analysis show reduced IFITM1 in EBV-positive ECs and a negative correlation between IFITM1 level and EBV copy number. IFITM1 depletion increases EBV infection and vice versa. Exogenous soluble IFITM1 effectively prevents EBV infection in vitro and in vivo. Furthermore, three-dimensional structure prediction and site-directed mutagenesis demonstrate that IFITM1 interacts with EphA2 via its two specific residues, competitively blocking EphA2 binding to EBV glycoproteins. Finally, YTHDF3, an m6A reader, suppresses IFITM1 via degradation-related DEAD-box protein 5 (DDX5). Thus, this study underscores IFITM1's crucial role in blocking EphA2-mediated EBV entry into ECs, indicating its potential in preventing EBV infection.


Asunto(s)
Antígenos de Diferenciación , Efrina-A2 , Células Epiteliales , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Receptor EphA2 , Internalización del Virus , Humanos , Herpesvirus Humano 4/fisiología , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Células Epiteliales/virología , Células Epiteliales/metabolismo , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/metabolismo , Receptor EphA2/metabolismo , Efrina-A2/metabolismo , Efrina-A2/genética , Antígenos de Diferenciación/metabolismo , Antígenos de Diferenciación/genética , Animales , Células HEK293 , Unión Proteica , Ratones , Línea Celular
13.
Front Microbiol ; 15: 1375120, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38605715

RESUMEN

Filamentous fungi play a crucial role in environmental pollution control, protein secretion, and the production of active secondary metabolites. The evolution of gene editing technology has significantly improved the study of filamentous fungi, which in the past was laborious and time-consuming. But recently, CRISPR-Cas systems, which utilize small guide RNA (sgRNA) to mediate clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas), have demonstrated considerable promise in research and application for filamentous fungi. The principle, function, and classification of CRISPR-Cas, along with its application strategies and research progress in filamentous fungi, will all be covered in the review. Additionally, we will go over general matters to take into account when editing a genome with the CRISPR-Cas system, including the creation of vectors, different transformation methodologies, multiple editing approaches, CRISPR-mediated transcriptional activation (CRISPRa) or interference (CRISPRi), base editors (BEs), and Prime editors (PEs).

14.
Neuroimage Clin ; 42: 103608, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38653131

RESUMEN

Magnetoencephalography (MEG) is a non-invasive technique that can precisely capture the dynamic spatiotemporal patterns of the brain by measuring the magnetic fields arising from neuronal activity along the order of milliseconds. Observations of brain dynamics have been used in cognitive neuroscience, the diagnosis of neurological diseases, and the brain-computer interface (BCI). In this study, we outline the basic principle, signal processing, and source localization of MEG, and describe its clinical applications for cognitive assessment, the diagnoses of neurological diseases and mental disorders, preoperative evaluation, and the BCI. This review not only provides an overall perspective of MEG, ranging from practical techniques to clinical applications, but also enhances the prevalent understanding of neural mechanisms. The use of MEG is expected to lead to significant breakthroughs in neuroscience.

15.
J Robot Surg ; 18(1): 186, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38683492

RESUMEN

The study aims to assess the available literature and compare the perioperative outcomes of robotic-assisted partial nephrectomy (RAPN) for posterior-lateral renal tumors using transperitoneal (TP) and retroperitoneal (RP) approaches. Systematically searched the Embase, PubMed, and Cochrane Library databases for literature. Eligible studies were those that compared TP-RAPN and RP-RAPN for posterior-lateral renal tumors. The data from the included studies were analyzed and summarized using Review Manager 5.3, which involved comparing baseline patient and tumor characteristics, intraoperative and postoperative outcomes, and oncological outcomes. The analysis included five studies meeting the inclusion criteria, with a total of 1440 patients (814 undergoing RP-RAPN and 626 undergoing TP-RAPN). Both groups showed no significant differences in age, gender, BMI, R.E.N.A.L. score, and tumor size. Notably, compared to TP-RAPN, the RP-RAPN group demonstrated shorter operative time (OT) (MD: 17.25, P = 0.01), length of hospital stay (LOS) (MD: 0.37, P < 0.01), and lower estimated blood loss (EBL) (MD: 15.29, P < 0.01). However, no significant differences were found between the two groups in terms of warm ischemia time (WIT) (MD: -0.34, P = 0.69), overall complications (RR: 1.25, P = 0.09), major complications (the Clavien-Dindo classification ≥ 3) (RR: 0.97, P = 0.93), and positive surgical margin (PSM) (RR: 1.06, P = 0.87). The systematic review and meta-analysis suggests RP-RAPN may be more advantageous for posterior-lateral renal tumors in terms of OT, EBL, and LOS, but no significant differences were found in WIT, overall complications, major complications, and PSM. Both surgical approaches are safe, but a definitive advantage remains uncertain.


Asunto(s)
Neoplasias Renales , Laparoscopía , Tiempo de Internación , Nefrectomía , Tempo Operativo , Procedimientos Quirúrgicos Robotizados , Femenino , Humanos , Masculino , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Neoplasias Renales/cirugía , Laparoscopía/métodos , Tiempo de Internación/estadística & datos numéricos , Nefrectomía/métodos , Peritoneo/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Procedimientos Quirúrgicos Robotizados/métodos , Resultado del Tratamiento
16.
Front Microbiol ; 15: 1378070, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38655081

RESUMEN

Porcine epidemic diarrhea virus (PEDV) has caused huge economic losses to the pig industry. Yeast polysaccharides (YP) has been used as a feed additive in recent years and poses good anti-inflammatory and antiviral effects. The present study aimed to explore the protective effect of YP on intestinal damage in PEDV-infected piglets. Eighteen 7-day-old piglets with similar body weights were randomly divided into three groups: Control group (basal diet), PEDV group (basal diet), and PEDV+YP group (basal diet +20 mg/kg BW YP), six replicates per group and one pig per replicate. Piglets in PEDV group and PEDV+YP group were orally given PEDV (dose: 1 × 106 TCID50) at 19:30 PM on the 8th day of the experiment. The control group received the same volume of PBS solution. Weight was taken on an empty stomach in the morning of the 11th day, blood was collected and then anesthetic was administered with pentobarbital sodium (50 mg/kg·BW) by intramuscular injection, and samples were slaughtered after the anesthetic was complete. The results showed that YP could alleviate the destruction of intestinal villus morphology of piglets caused by PEDV. Meanwhile, PEDV infection can reduce the activity of glutathione peroxidase, superoxide dismutase and catalase, and increase the content of malondialdehyde. YP can improve the antioxidative capacity in the serum and small intestine of PEDV-infected piglets. In addition, YP inhibited the replication of PEDV in the jejunum ileum and colon. Moreover, YP can regulate the mRNA levels of inflammatory genes (IL-1ß and iNOS) and lipid metabolic genes (APOA4 and APOC3) in the small intestine. In summary, YP could inhibit virus replicates, improve intestinal morphology, enhance antioxidant capacity, relieve inflammation and regulate the metabolism of the intestine in PEDV-infected piglets.

17.
Front Pharmacol ; 15: 1364616, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38659578

RESUMEN

As the quality of life improves, the incidence of diabetes mellitus and its microvascular complications (DMC) continues to increase, posing a threat to people's health and wellbeing. Given the limitations of existing treatment, there is an urgent need for novel approaches to prevent and treat DMC. Autophagy, a pivotal mechanism governing metabolic regulation in organisms, facilitates the removal of dysfunctional proteins and organelles, thereby sustaining cellular homeostasis and energy generation. Anomalous states in pancreatic ß-cells, podocytes, Müller cells, cardiomyocytes, and Schwann cells in DMC are closely linked to autophagic dysregulation. Natural products have the property of being multi-targeted and can affect autophagy and hence DMC progression in terms of nutrient perception, oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis. This review consolidates recent advancements in understanding DMC pathogenesis via autophagy and proposes novel perspectives on treating DMC by either stimulating or inhibiting autophagy using natural products.

18.
World J Gastrointest Oncol ; 16(4): 1268-1280, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38660670

RESUMEN

BACKGROUND: Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years. However, the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study. In order to determine the association between adverse reaction factors and prognosis, the aim of this study was to conduct a systematic prognostic analysis. By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy, a nomogram model will be established to predict the survival status of patients more accurately. AIM: To explore the characteristics and predictors of immune-related adverse reactions (irAEs) in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1 (PD-1) inhibitors and to analyze the correlation between irAEs and patient prognosis. METHODS: A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected. Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred. Clinical features, manifestations, and prognosis of irAEs in the two groups were collected and analyzed. A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs, and the prediction model of irAEs was established. The receiver operating characteristic (ROC) curve was used to evaluate the ability of different indicators to predict irAEs. A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis. The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients. RESULTS: A total of 132 patients were followed up, of whom 63 (47.7%) developed irAEs. We looked at the two groups' clinical features and found that the two groups were statistically different in age ≥ 65 years, Ki-67 index, white blood cell count, neutrophil count, and regulatory T cell (Treg) count (all P < 0.05). Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence (P = 0.030). The ROC curve indicated that Treg + Ki-67 + age (≥ 65 years) combined could predict irAEs well (area under the curve = 0.753, 95% confidence interval: 0.623-0.848, P = 0.001). Results of the Kaplan-Meier survival curve showed that progression-free survival (PFS) was longer in the irAEs group than in the non-irAEs group (P = 0.001). Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS (P = 0.006). CONCLUSION: The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy. irAEs can affect the patients' PFS and result in longer PFS. Treg + Ki-67 + age (≥ 65 years old) combined can better predict the occurrence of adverse reactions.

19.
Front Pharmacol ; 15: 1328977, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38645561

RESUMEN

Introduction: P. candolleana Wight et Arn. Is a traditional Chinese herbal medicine used by the Gelao nationality in southwest China, has been historically applied to treat various gastrointestinal disorders. Despite its traditional usage, scientific evidence elucidating its efficacy and mechanisms in treating ulcerative colitis (UC) remains sparse. This study aimed to determine the quality and chemical composition of Pimpinella candolleana and to identify its potential therapeutic targets and mechanisms in acetic acid-induced ulcerative colitis (UC) rats through integrated approaches. Methods: Morphological and microscopic characteristics, thin layer chromatography (TLC) identification, and quantitative analysis of P. candolleana were performed. UPLC-Q-TOF-MS, network pharmacology, and molecular docking were used to identify its chemical composition and predict its related targets in UC. Furthermore, a rat model was established to evaluate the therapeutic effect and potential mechanism of P. candolleana on UC. Results: Microscopic identification revealed irregular and radial arrangement of the xylem in P. candolleana, with a light green cross-section and large medullary cells. UPLC-Q-TOF-MS analysis detected and analyzed 570 metabolites, including flavonoids, coumarins, and terpenoids. Network pharmacology identified 12 effective components and 176 target genes, with 96 common targets for P. candolleana-UC, including quercetin, luteolin, and nobiletin as key anti-inflammatory components. GO and KEGG revealed the potential involvement of their targets in RELA, JUN, TNF, IKBKB, PTGS2, and CHUK, with action pathways such as PI3K-Akt, TNF, IL-17, and apoptosis. Molecular docking demonstrated strong affinity and binding between these key components (quercetin, luteolin, and nobiletin) and the key targets of the pathway, including JUN and TNF. Treatment with P. candolleana improved body weight loss, the disease activity index, and colonic histological damage in UC rats. Pimpinella candolleana also modulated the levels of IL-2 and IL-6 in UC rats, reduced the expression of pro-inflammatory cytokines such as IL-6, MAPK8, TNF-α, CHUK, and IKBKB mRNA, and decreased the expression of TNF, IKBKB, JUN, and CHUK proteins in the colon of UC rats, thereby reducing inflammation and alleviating UC symptoms. Conclusion: P. candolleana exerts its protective effect on UC by reducing the expression of proinflammatory cytokines and inhibiting inflammation, providing scientific evidence for its traditional use in treating gastrointestinal diseases. This study highlights the potential of P. candolleana as a natural therapeutic agent for UC and contributes to the development of novel medicines for UC treatment.

20.
Sci Rep ; 14(1): 8327, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594340

RESUMEN

Urban water bodies can effectively mitigate the urban heat island effect and thus enhance the climate resilience of urban areas. The cooling effect of different water bodies varies, however, the cooling heterogeneity of different sections of a single watercourse or river network is rarely considered. Based on various satellite images, geospatial approaches and statistical analyses, our study confirmed the cooling heterogeneity from spatial and seasonal perspectives of the Suzhou Outer-city River in detail in the urban area of Suzhou, China. The cooling effect of the river was observed in the daytime in four seasons, and it is strongest in summer, followed by spring and autumn, and weakest in winter. The combination of the width of the river reach, the width and the NDVI value of the adjacent green space can explain a significant part of the cooling heterogeneity of the different river sections in different seasons. Land surface temperature (LST) variations along the river are more related to the width of the river reach, but the variations of the cooling distance are more related to the adjacent green space. The cooling effect of a river reach could be enhanced if it is accompanied by green spaces. In addition, the cooling effect of a looping river is stronger on the inside area than on the outside. The methodology and results of this study could help orient scientific landscape strategies in urban planning for cooler cities.

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