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1.
J Cell Mol Med ; 28(5): e17895, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37525480

RESUMEN

Immune checkpoint inhibitors (ICIs) therapy have revolutionized advanced lung cancer care. Interestingly, the host responses for patients received ICIs therapy are distinguishing from those with cytotoxic drugs, showing potential initial transient worsening of disease burden, pseudoprogression and delayed time to treatment response. Thus, a new imaging criterion to evaluate the response for immunotherapy should be developed. ICIs treatment is associated with unique adverse events, including potential life-threatening immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis) if treated patients are not managed promptly. Currently, the diagnosis and clinical management of ICI-pneumonitis remain challenging. As the clinical manifestation is often nonspecific, computed tomography (CT) scan and X-ray films play important roles in diagnosis and triage. This article reviews the complications of immunotherapy in lung cancer and illustrates various radiologic patterns of ICI-pneumonitis. Additionally, it is tried to differentiate ICI-pneumonitis from other pulmonary pathologies common to lung cancer such as radiation pneumonitis, bacterial pneumonia and coronavirus disease of 2019 (COVID-19) infection in recent months. Maybe it is challenging to distinguish radiologically but clinical presentation may help.

2.
J Cogn Neurosci ; 35(1): 90-110, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36166300

RESUMEN

The hippocampus plays a critical role in supporting episodic memory, in large part by binding together experiences and items with surrounding contextual information. At present, however, little is known about the roles of different hippocampal subfields in supporting this item-context binding. To address this question, we constructed a task in which items were affiliated with differing types of context-cognitive associations that vary at the local, item level and membership in temporally organized lists that linked items together at a global level. Participants made item recognition judgments while undergoing high-resolution fMRI. We performed voxel pattern similarity analyses to answer the question of how human hippocampal subfields represent retrieved information about cognitive states and the time at which a past event took place. As participants recollected previously presented items, activity patterns in the CA23DG subregion carried information about prior cognitive states associated with these items. We found no evidence to suggest reinstatement of information about temporal context at the level of list membership, but exploratory analyses revealed representations of temporal context at a coarse level in conjunction with representations of cognitive contexts. Results are consistent with characterizations of CA23DG as a critical site for binding together items and contexts in the service of memory retrieval.


Asunto(s)
Hipocampo , Memoria Episódica , Humanos , Hipocampo/diagnóstico por imagen , Recuerdo Mental , Reconocimiento en Psicología , Imagen por Resonancia Magnética
3.
BMC Med Imaging ; 22(1): 119, 2022 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-35787673

RESUMEN

OBJECT: To explore the feasibility and clinical application of AI -assisted compressed sensing (ACS) technology in kidney MR imaging. METHODS: 33 patients were enrolled in this study, affiliated to our hospital from September 2020 to April 2021. The patients underwent T2-weighed sequences of both the ACS scan and the conventional respiratory navigator (NAVI) scan. We evaluated the subjective image quality scores, including the sharpness of image edge, artifact and the overall image quality, and compared the objective image quality indicators such as scanning time, signal-to-noise ratio (SNR), and contrast signal-to-noise ratio (CNR). The Wilcoxon's rank sum test and the paired t test were used to compare the image quality between ACS and NAVI groups. The p-value less than 0.05 indicated a statistically significant difference. RESULTS: The edge sharpness of the ACS group was significant lower than that of the NAVI group (p < 0.01), however, there were no significant differences in the artifact and the overall rating of image quality between the two groups (p > 0.05). In terms of the objective image quality scores, the scanning time of the ACS group is significantly lower than that of control group. The SNR and CNR of ACS group were significantly higher than those of NAVI group (SNR:3.63 ± 0.76 vs 3.04 ± 0.44, p < 0.001; CNR: 14.44 ± 4.53 vs 12.05 ± 3.32, p < 0.001). In addition, the subjective and objective measurement results of the two radiologists were in good agreement (ICC = 0.61-0.88). CONCLUSION: ACS technology has obvious advantages when applied to kidney MR imaging, which can realize ultra-fast MR imaging. The images can be acquired with a single breath-hold (17 s), which greatly shortens the scanning time. Moreover, the image quality is equal to or better than the conventional technology, which can meet the diagnostic requirements. Thus, it has obvious advantages in diagnosis for kidney disease patients with different tolerance levels for the clinical promotion.


Asunto(s)
Riñón , Imagen por Resonancia Magnética , Inteligencia Artificial , Estudios de Factibilidad , Humanos , Riñón/diagnóstico por imagen , Tecnología
4.
J Neurosci ; 40(11): 2343-2356, 2020 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-32019830

RESUMEN

Goal-directed behavior can benefit from proactive adjustments of cognitive control that occur in anticipation of forthcoming cognitive control demands (CCD). Predictions of forthcoming CCD are thought to depend on learning and memory in two ways: First, through direct experience, associative encoding may link previously experienced CCD to its triggering item, such that subsequent encounters with the item serve to cue retrieval of (i.e., predict) the associated CCD. Second, in the absence of direct experience, pattern completion and mnemonic integration mechanisms may allow CCD to be generalized from its associated item to other items related in memory. While extant behavioral evidence documents both types of CCD prediction, the neurocognitive mechanisms giving rise to these predictions remain largely unexplored. Here, we tested two hypotheses: (1) memory-guided predictions about CCD precede control adjustments due to the actual CCD required; and (2) generalization of CCD can be accomplished through integration mechanisms that link partially overlapping CCD-item and item-item associations in memory. Supporting these hypotheses, the temporal dynamics of theta and alpha power in human electroencephalography data (n = 43, 26 females) revealed that an associative CCD effect emerges earlier than interaction effects involving actual CCD. Furthermore, generalization of CCD from one item (X) to another item (Y) was predicted by a decrease in alpha power following the presentation of the X-Y pair. These findings advance understanding of the mechanisms underlying memory-guided adjustments of cognitive control.SIGNIFICANCE STATEMENT Cognitive control adaptively regulates information processing to align with task goals. Experience-based expectations enable adjustments of control, leading to improved performance when expectations match the actual control demand required. Using EEG, we demonstrate that memory for past cognitive control demand proactively guides the allocation of cognitive control, preceding adjustments of control triggered by the demands of the present environment. Furthermore, we demonstrate that learned cognitive control demands can be generalized through mnemonic integration processes, enabling the spread of expectations about cognitive control demands to items associated in memory. We reveal that this generalization is linked to decreased alpha oscillation in medial frontal channels. Collectively, these findings provide new insights into how memory-control interactions facilitate goal-directed behavior.


Asunto(s)
Aprendizaje por Asociación/fisiología , Cognición/fisiología , Memoria/fisiología , Adaptación Psicológica , Adolescente , Adulto , Ritmo alfa/fisiología , Mapeo Encefálico , Señales (Psicología) , Electroencefalografía , Femenino , Objetivos , Humanos , Masculino , Desempeño Psicomotor/fisiología , Tiempo de Reacción , Test de Stroop , Ritmo Teta/fisiología , Factores de Tiempo , Adulto Joven
5.
Bioorg Med Chem ; 50: 116482, 2021 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-34757292

RESUMEN

Treatment options for the progression of pulmonary fibrosis (PF), which ultimately causes respiratory failure, are limited. According to recent studies, recombinant human relaxin is potentially therapeutic against fibrosis and contraction during pulmonary damage. However, the production of recombinant H2 relaxin is laborious and expensive, limiting its extensive application. Thankfully, alternative research has revealed that treatment with a single-chain peptide of relaxin attenuates organ fibrosis in rodent models too, with the production of a single-chain peptide of relaxin simple and cheap; it could be therapeutic against idiopathic pulmonary fibrosis. Here, we explored the probable inhibiting effects of B7, a B chain of recombinant human relaxin, on bleomycin-induced pulmonary inflammation. Inhaled B7 efficiently reduced the number of inflammatory leukocytes and neutrophils in the bronchoalveolar lavage fluid of mice with bleomycin-induced PF, significantly improved the structure of the damaged alveolar, reduced collagen deposition, suppressed the main pathological features of idiopathic pulmonary fibrosis, i.e. the expression of both pulmonary α-smooth muscle actin and pulmonary vimentin, and inhibited the transcription of inflammation and collagen deposition-related mRNAs, including fibronectin, α-smooth muscle actin (α-SMA), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and alpha-1 type 1 collagen (Col-1a), and the expression of inflammation-related proteins, such as IL-1ß, IL-6, chemokines (KC), TIMP metallopeptidase inhibitor 1 (TIMP-1), and hydroxyproline (Hyp). Overall, our findings suggest that inhaled B7 exerts beneficial effects against pulmonary fibrosis via attenuating inflammation. It could be developed into a simple, highly effective therapeutic approach for pulmonary fibrosis.


Asunto(s)
Fibrosis Pulmonar/tratamiento farmacológico , Relaxina/farmacología , Administración por Inhalación , Animales , Bleomicina/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Ratones , Ratones Endogámicos ICR , Estructura Molecular , Fibrosis Pulmonar/inducido químicamente , Relaxina/administración & dosificación , Relación Estructura-Actividad
6.
Mov Disord ; 32(4): 487-497, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28343366

RESUMEN

In Parkinson's disease (PD), dopamine depletion causes major changes in the brain, resulting in the typical cardinal motor features of the disease. PD neuropathology has been restricted to postmortem examinations, which are limited to only a single time of PD progression. Models of PD in which dopamine tone in the brain is chemically or physically disrupted are valuable tools in understanding the mechanisms of the disease. The basal ganglia have been well studied in the context of PD, and circuit changes in response to dopamine loss have been linked to the motor dysfunctions in PD. However, the etiology of the cognitive dysfunctions that are comorbid in PD patients has remained unclear until now. In this article, we review recent studies exploring how dopamine depletion affects the motor cortex at the synaptic level. In particular, we highlight our recent findings on abnormal spine dynamics in the motor cortex of PD mouse models through in vivo time-lapse imaging and motor skill behavior assays. In combination with previous studies, a role of the motor cortex in skill learning and the impairment of this ability with the loss of dopamine are becoming more apparent. Taken together, we conclude with a discussion on the potential role for the motor cortex in PD, with the possibility of targeting the motor cortex for future PD therapeutics. © 2017 International Parkinson and Movement Disorder Society.


Asunto(s)
Aprendizaje/fisiología , Corteza Motora/patología , Plasticidad Neuronal/fisiología , Enfermedad de Parkinson/patología , Animales , Modelos Animales de Enfermedad , Dopaminérgicos/farmacología , Dopaminérgicos/uso terapéutico , Humanos , Corteza Motora/efectos de los fármacos , Trastornos de la Destreza Motora/etiología , Plasticidad Neuronal/efectos de los fármacos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico
7.
Biol Proced Online ; 18: 5, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26839516

RESUMEN

BACKGROUND: One of the most notable recent advances in electron microscopy (EM) was the development of genetically-encoded EM tags, including the fluorescent flavoprotein Mini-SOG (Mini-Singlet Oxygen Generator). Mini-SOG generates good EM contrast, thus providing a viable alternative to technically-demanding methods such as immuno-electron microcopy (immuno-EM). Based on the Mini-SOG technology, in this paper, we describe the construction, validation and optimization of a series of vectors which allow expression of Mini-SOG in the Drosophila melanogaster genetic model system. FINDINGS: We constructed a Mini-SOG tag that has been codon-optimized for expression in Drosophila (DMS tag) using PCR-mediated gene assembly. The photo-oxidation reaction triggered by DMS was then tested using these vectors in Drosophila cell lines. DMS tag did not affect the subcellular localization of the proteins we tested. More importantly, we demonstrated the utility of the DMS tag for EM in Drosophila by showing that it can produce robust photo-oxidation reactions in the presence of blue light and the substrate DAB; the resultant electron micrographs contain electron-dense regions corresponding to the protein of interest. The vectors we generated allow protein tagging at both termini, for constitutive and inducible protein expression, as well as the generation of transgenic lines by P-element transformation. CONCLUSIONS: We demonstrated the feasibility of Mini-SOG tagging in Drosophila. The constructed vectors will no doubt be a useful molecular tool for genetic tagging to facilitate high-resolution localization of proteins in Drosophila by electron microscopy.

8.
Neurobiol Learn Mem ; 134 Pt A: 123-134, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-26805590

RESUMEN

Regional differences in large-scale connectivity have been proposed to underlie functional specialization along the anterior-posterior axis of the medial temporal lobe (MTL), including the hippocampus (HC) and the parahippocampal gyrus (PHG). However, it is unknown whether functional connectivity (FC) can be used reliably to parcellate the human MTL. The current study aimed to differentiate subregions of the HC and the PHG based on patterns of whole-brain intrinsic FC. FC maps were calculated for each slice along the longitudinal axis of the PHG and the HC. A hierarchical clustering algorithm was then applied to these data in order to group slices according to the similarity of their connectivity patterns. Surprisingly, three discrete clusters were identified in the PHG. Two clusters corresponded to the parahippocampal cortex (PHC) and the perirhinal cortex (PRC), and these regions showed preferential connectivity with previously described posterior-medial and anterior-temporal networks, respectively. The third cluster corresponded to an anterior PRC region previously described as area 36d, and this region exhibited preferential connectivity with auditory cortical areas and with a network involved in visceral processing. The three PHG clusters showed different profiles of activation during a memory-encoding task, demonstrating that the FC-based parcellation identified functionally dissociable sub-regions of the PHG. In the hippocampus, no sub-regions were identified via the parcellation procedure. These results indicate that connectivity-based methods can be used to parcellate functional regions within the MTL, and they suggest that studies of memory and high-level cognition need to differentiate between PHC, posterior PRC, and anterior PRC.


Asunto(s)
Conectoma/métodos , Hipocampo/fisiología , Procesamiento de Imagen Asistido por Computador , Giro Parahipocampal/fisiología , Lóbulo Temporal/fisiología , Adulto , Femenino , Hipocampo/diagnóstico por imagen , Humanos , Aprendizaje/fisiología , Imagen por Resonancia Magnética , Masculino , Giro Parahipocampal/diagnóstico por imagen , Lóbulo Temporal/diagnóstico por imagen , Adulto Joven
9.
Adv Exp Med Biol ; 923: 393-399, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27526168

RESUMEN

The function of the brain neural circuit is highly dependent on oxygen supply. Imaging the precise oxygen distribution and dynamics are critical for understanding the relationship between neuronal activity and oxygen dynamics of the nearby capillaries. Here, we develop fast acousto-optic scanning two-photon microscopy. Combined with oxygen probes, such as PtP-C343, we can monitor oxygen dynamics at the submicron level by this real-time microscopy. In this fast acousto-optic scanning microscopy, an acousto-optic deflector (AOD), an inertia-less scanner, is used to scan the femtosecond laser. A cylindrical lens is used to compensate the 'cylindrical lens effect' of AOD and a prism is used to compensate the chromatic dispersion of AOD. An electro-optical modulator (EOM) and a sCMOS camera are gated to measure the phosphorescence lifetime. With a 40× water objective lens, this set-up can image a 100 µm × 100 µm field of view at a speed of 20 frames per second and a 25 µm × 8 µm field of view at a speed of 500 frames per second. This real-time two-photon microscopy is expected to be a good tool for observing and recording the precise rapid oxygen dynamics in the cerebral cortex, which will facilitate studies of oxygen metabolism in neurosciences.


Asunto(s)
Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/metabolismo , Circulación Cerebrovascular , Rayos Láser , Lentes , Microscopía Acústica/instrumentación , Microscopía de Fluorescencia por Excitación Multifotónica/instrumentación , Óptica y Fotónica/instrumentación , Consumo de Oxígeno , Oxígeno/sangre , Animales , Biomarcadores/sangre , Diseño de Equipo , Colorantes Fluorescentes/metabolismo , Cinética , Ratones
10.
J Exp Bot ; 65(20): 5759-69, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25086591

RESUMEN

The structural characteristics and component differences of proanthocyanidins in brown and white cotton fibres were identified by nuclear magnetic resonance (NMR) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analyses. Proanthocyanidins in brown and white cotton fibres were found to contain mainly procyanidin (PC) and prodelphidin (PD) units with 2, 3-cis form (epigallocatechin and epicatechin). However, part of the proanthocyanidins in the white cotton fibres were modified by acylation and were constitutively different from the proanthocyanidins in brown cotton fibres. The relative amount of PD was similar to that of PC in white cotton fibres, while proanthocyanidins in brown cotton fibres consisted mainly of PD units with a relative ratio of 9:1. In brown cotton fibres, the proanthocyanidin monomeric composition was consistent with the expression profiles of proanthocyanidin synthase genes, suggesting that anthocyanidin reductase represented the major flow of the proanthocyanidin biosynthesis pathway. In addition, the structural characteristics and component differences of proanthocanidins in brown and white cotton fibres suggested that quinones, the oxidation products of proanthocyanidins, were the direct contributors to colour development in brown cotton fibre. This was demonstrated by vanillin-HCl staining and Borntrager's test. Collectively, these data demonstrated that the biosynthesis of proanthocyanidins is a crucial pigmentation process in brown cotton fibre, and that quinones may represent the main pigments contributing to formation of the the brown colour. This study revealed the molecular basis of pigmentation in brown cotton fibres, and provided important insights for genetic manipulation of pigment production in cotton fibres.


Asunto(s)
Gossypium/genética , Pigmentación , Proantocianidinas/metabolismo , Antocianinas/metabolismo , Vías Biosintéticas , Fibra de Algodón , Regulación de la Expresión Génica de las Plantas , Gossypium/química , Gossypium/enzimología , Espectroscopía de Resonancia Magnética , Peso Molecular , Oxidorreductasas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proantocianidinas/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
11.
iScience ; 27(2): 108885, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38313051

RESUMEN

Resistance to cisplatin (cis-dichlorodiamineplatinum, DDP) in ovarian cancer is a significant clinical challenge. Epigallocatechin-3-gallate (EGCG) has shown promise in cancer therapy. However, its effects on DDP-resistant ovarian cancer remain understudied. This study aims to assess the impact of EGCG on DDP-resistant cells and elucidate the associated molecular mechanisms. DDP-resistant cell lines were utilized for biological characterization. EGCG effectively inhibited proliferation, mobility, and induced apoptosis in OC/DDP cells. It downregulated the expression of S100A4 and NF-κB while upregulating p53 expression. These effects were reversed upon overexpression of S100A4 or NF-κB. In vivo experiments confirmed tumor inhibition and KI67 inhibition by EGCG. Moreover, EGCG downregulated the expression of S100A4 and NF-κB while upregulating p53 in xenograft mice compared to those without EGCG treatment. This study suggests that EGCG suppresses cancer progression through the S100A4/NF-κB signaling pathway, involving interaction with p53. EGCG holds potential as an anticancer candidate for OC/DDP.

12.
Heliyon ; 10(1): e22817, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38169794

RESUMEN

Objective: To evaluate the applicability of artificial intelligence-assisted compressed sensing (ACS) to anal fistula magnetic resonance imaging (MRI). Methods: 51 patients were included in this study and underwent T2-weighted sequence of MRI examinations both with ACS and without ACS technology in a 3.0 T MR scanner. Subjective image quality scores, and objective image quality-related metrics including scanning time, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR), were evaluated and statistically compared between the images collected with and without ACS. Results: No significant difference in the subjective image quality of lesion conspicuity was observed between the two groups. However, ACS MRI decreased the acquisition time with regard to control group (74.00 s vs. 156.00 s). Besides, SNR of perianal and muscle in the ACS group was significantly higher than that of the control group (164.07 ± 33.35 vs 130.81 ± 29.10, p < 0.001; 109.87 ± 22.01 vs 87.61 ± 17.95, p < 0.001; respectively). The CNR was significantly higher in the ACS group than in the control group (54.02 ± 23.98 vs 43.20 ± 21.00; p < 0.001). Moreover, the accuracy rate of the ACS groups in evaluating the direction and internal opening of the fistula was 88.89 %, exactly the same as that of the control group. Conclusion: We demonstrated the applicability of using ACS to accelerate MR of anal fistulas with improved SNR and CNR. Meanwhile, the accuracy rates of the ACS group and the control were equivalent in evaluating the direction and internal opening of the fistula, based on the results of surgical exploration.

13.
Clin Case Rep ; 11(10): e8036, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37867543

RESUMEN

Key Clinical Message: Pheochromocytoma crisis accompanied by multi-organ failure necessitates prompt and comprehensive interventions, including VA-ECMO, CRRT, and others. Successful laparoscopic tumor resection promotes favorable outcomes and recovery. Abstract: Pheochromocytoma crisis is commonly associated with high mortality, high surgical risk, and rapidly fatal complications. This article presented successful treatments and nursing experiences in a patient with pheochromocytoma who developed cardiogenic shock and multiple organ failure. We report a case study of a 32-year-old female patient who experienced pheochromocytoma crisis accompanied by multiple organ failure. Initial assessment of bedside echocardiography revealed an extremely low left ventricular ejection fraction of 8%. The patient was promptly resuscitated though tracheal intubation and venoarterial extracorporeal membrane oxygenation (VA-ECMO), in conjunction with continuous renal replacement therapy (CRRT), alpha-blockers, beta-blockers, and other pharmacological interventions to manage blood pressure and heart rate. These interventions resulted in a remarkable increase in the left ventricular ejection fraction of 67%. However, the patient subsequently developed severe sepsis, which may have been caused by the intubation procedure, necessitating the discontinuation of VA-ECMO while maintaining CRRT. Close monitoring of plasma catecholamine metabolite level, hemodynamic index, inflammatory marker, liver and kidney functions, and electrolytes during CRRT support allows for evaluating the efficacy of these measures and assessing the impact of CRRT on pheochromocytoma crisis. Eventually, the patient successfully underwent laparoscopic resection of a large pheochromocytoma, leading to favorable prognosis and a successful recovery. Continuous blood purification therapy can effectively eliminate catecholamines and their byproducts from the plasma, stabilize hemodynamics, improve heart, liver, and kidney functions, significantly reduce inflammatory cytokine levels significantly, and extend the surgical window for patients.

14.
Front Immunol ; 14: 1274431, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38022654

RESUMEN

Background: Immunotherapy is significantly revolutionizing cancer treatment and demonstrating promising efficacy in gastric cancer (GC) patients. However, only a subset of patients could derive benefits from targeted monoclonal antibody therapy against programmed death receptor 1 (PD-1). This study aims to identify suitable serum cytokines and blood cell ratios as predictive biomarkers to aid in the selection of GC patients likely to benefit from PD-1 inhibitors. Materials and methods: This retrospective study included 41 GC patients who received PD-1 inhibitors combined with chemotherapy, 36 GC patients treated solely with chemotherapy, and 33 healthy controls. The study assessed the levels of seven cytokines: interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and various inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), total lymphocyte count (TLC), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). Measurements were obtained using the inpatient system. Univariate and multivariate Cox regression analyses were performed to evaluate the predictive significance of these hematologic parameters for clinical outcomes. Results: Levels of IL-6, IL-10, TNF-α, NLR, and PLR were significantly elevated in GC patients compared to healthy controls, while TLC and LMR were higher in the control group. Among the 41 patients receiving PD-1 inhibitors and chemotherapy, baseline IL-2 was associated with OS and PFS. Additionally, IL-6 and IL-17A correlated with OS, while NLR was linked to PFS (all P<0.05). These factors were identified as independent prognostic indicators in both univariate and multivariate analyses. Furthermore, almost all cytokine levels increased following the initiation of PD-1 inhibitor treatment. Conclusions: The introduction of PD-1 inhibitors alongside chemotherapy in GC impacts serum cytokine levels. IL-2, IL-6, IL-17A, and NLR exhibit potential as reliable circulating predictive biomarkers for identifying patients who may benefit from PD-1 inhibitors combined with chemotherapy.


Asunto(s)
Neutrófilos , Neoplasias Gástricas , Humanos , Neutrófilos/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Interleucina-10 , Interleucina-2/uso terapéutico , Interleucina-17 , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Estudios Retrospectivos , Citocinas/uso terapéutico , Factor de Necrosis Tumoral alfa/uso terapéutico , Interleucina-6 , Linfocitos/patología , Biomarcadores
15.
Elife ; 122023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36786678

RESUMEN

As we learn, dynamic memory processes build structured knowledge across our experiences. Such knowledge enables the formation of internal models of the world that we use to plan, make decisions, and act. Recent theorizing posits that mnemonic mechanisms of differentiation and integration - which at one level may seem to be at odds - both contribute to the emergence of structured knowledge. We tested this possibility using fMRI as human participants learned to navigate within local and global virtual environments over the course of 3 days. Pattern similarity analyses on entorhinal cortical and hippocampal patterns revealed evidence that differentiation and integration work concurrently to build local and global environmental representations, and that variability in integration relates to differences in navigation efficiency. These results offer new insights into the neural machinery and the underlying mechanisms that translate experiences into structured knowledge that allows us to navigate to achieve goals.


Asunto(s)
Objetivos , Hipocampo , Humanos , Memoria , Corteza Entorrinal , Imagen por Resonancia Magnética , Mapeo Encefálico/métodos
16.
ChemMedChem ; 18(12): e202300154, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37009677

RESUMEN

Investigations on praziquantel (PZQ) started fifty years ago by a cooperation between Bayer AG and Merck KGaA. Until today PZQ is the drug of choice for schistosomiasis in human medicine and used in many combinations with antinematode drugs in veterinary medicine. The Sm.TRPMPZQ , a Ca2+ -permeable transient receptor potential (TRP) channel, has been discovered as primary target of PZQ during the last decade. Furthermore, there is a short overview of routes of large-scale synthesis of racemic and pure (R)-PZQ. Until now racemic PZQ is used in veterinary and human medicine. In 2012 the Pediatric Praziquantel Consortium started PZQ chemistry and process development of pure (R)-PZQ for human application. It is hoped that (R)-PZQ will become available for pediatric use soon. The knowledge of the binding pocket of PZQ in Sm.TRPMPZQ allows to design synthesis of PZQ-derivatives of the next generation for a target-site directed screening. A similar screening should also be started for Fasciola hepatica TRPMPZQ .


Asunto(s)
Esquistosomiasis , Canales Catiónicos TRPM , Humanos , Niño , Praziquantel/farmacología , Praziquantel/metabolismo , Esquistosomiasis/tratamiento farmacológico
17.
Front Oncol ; 12: 991485, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36483032

RESUMEN

Background: Given the mortality benefit of low-dose computed tomography (LDCT) screening on high-risk populations, the retrospective investigation intended to identify the benefits of LDCT on lung cancer screening among the general demographic cohorts. Methods: We used an opportunistic screening with LDCT implemented during the pandemic in Wuhan to study the impact on subsequent thoracic surgeries, especially surgeries for lung cancer. Patients who received LDCT from October 1, 2019, to July 31, 2020, in three Triple-A accredited hospitals in Wuhan were included in the study. Relative week volumes of both surgeries before and after the chest LDCT screening were compared pairwise. The counts of surgeries for pulmonary nodules or masses, and corresponding pathological results among different gender and age groups were also compared. Result: The relative weekly volumes of thoracic surgery were significantly greater than those of stomach surgery after the opportunistic screening with LDCT. They were 33% (95% CI, 0.20-0.46; p<0. 001) higher than those of stomach surgery. For every 1,000 chest LDCT scans conducted in a given week, on average, 3.52(95% CI,0.56-6.49, p =0.03) thoracic surgeries were performed in the following week. After the implementation of opportunistic screening with LDCT, there was a higher percentage of young females with pulmonary nodule or mass (64.4% vs. 45.8%, p = 0.032). The fraction of lung cancer surgery in the treatment period was significantly greater than that in the control period (74.09% vs. 68.79%, p=0.007). There was a higher percentage of stage I lung cancer surgery in young and mid-age females than in the senior age group (64% vs. 53%, p= 0.05). Interpretation: Opportunistic screening with LDCT can advance the early diagnosis window of lung cancer in non-high-risk populations, especially young women who are easy to be ignored.

18.
Comput Biol Med ; 146: 105538, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35751192

RESUMEN

PURPOSE: To explore the application of computer-aided detection (CAD) software on automatically detecting nodules under standard-dose CT (SDCT) and low-dose CT (LDCT) scans with different parameters including definition modes and blending levels of adaptive statistical iterative reconstruction (ASIR), whose influence was important to optimize radiology workflow serving for clinical work. MATERIALS AND METHODS: 117 patients underwent SDCT and LDCT scans. The comprehensive performance of CAD in detect pulmonary nodules including under different ASIR blending levels (0%, 60%, and 80%) and high-definition (HD) or non-HD modes were assessed. The true positive (TP) rate, false positive (FP) rate and the sensitivity were recorded. RESULTS: The stand-alone sensitivity of CAD system was 78.03% (515/660) in SDCT images and 70.15% (456/650) on LDCT images (p < 0.05). The sensitivity of CAD system to pulmonary nodules under non-HD mode was higher than that under HD mode. The detectability of nodules in images reconstructed with 60% and 80% ASIR was found significantly superior to that with 0% ASIR (p < 0.001). The overall sensitivity of CAD system on LDCT images reconstructed with 60% ASIR under HD mode was greater than that with 0% ASIR (p < 0.05), but lower than that with 80% ASIR. However, under non-HD mode, CAD demonstrated a comparable performance on LDCT images reconstructed with 60% ASIR to those reconstructed with 80% ASIR. CONCLUSION: Using the CAD system to detect pulmonary nodules on LDCT images with appropriate levels of ASIR could maintain high diagnostic sensitivity while reducing the radiation dose, which is useful to optimize the radiology workflow.


Asunto(s)
Interpretación de Imagen Radiográfica Asistida por Computador , Tomografía Computarizada por Rayos X , Algoritmos , Humanos , Dosis de Radiación , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Cintigrafía , Programas Informáticos , Tomografía Computarizada por Rayos X/métodos
19.
Ann Clin Biochem ; 59(5): 338-346, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35549539

RESUMEN

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe disease with high mortality, and its primary cause is sepsis. The aim of this study was to detect and evaluate the role of Human epididymis protein 4 (HE4) in sepsis-related ARDS. METHODS: One hundred and twenty-three critically ill sepsis patients with/without ARDS and 102 healthy controls were enrolled in this study. Blood samples were collected upon admission for quantitative testing of HE4 by chemiluminescent microparticle immunoassay (CMIA). ROC curve analysis and Spearman's correlation analysis were conducted to determine the diagnostic and prognostic value of HE4. RESULTS: Compared with controls, the serum HE4 concentrations of sepsis patients were elevated, and levels in sepsis patients with ARDS were significantly higher (all p < 0.0001). Moreover, HE4 concentrations were strongly correlated with the clinical severity characteristics of sepsis patients, and ROC curve suggested that the AUC of HE4 applied to discriminate sepsis-ARDS patients from sepsis patients was 0.903. HE4 was also found to be a prognostic biomarker of clinical severity and 28-day mortality among critically ill sepsis patients. Logistic regression analysis showed that HE4 was an independent factor for diagnosis of ARDS. Meanwhile, ROC curve analysis showed that the cut-off value of serum HE4 to discriminate 28-day mortality from sepsis patients (AUC: 0.782) was 646.5 pmol/L. CONCLUSIONS: The concentration of serum HE4 in patients with sepsis-related ARDS was markedly increased and was significantly correlated with mortality, which suggests that serum HE4 could be a promising diagnostic and prognostic biomarker for ARDS in sepsis patients.


Asunto(s)
Síndrome de Dificultad Respiratoria , Sepsis , Biomarcadores , Enfermedad Crítica , Humanos , Pronóstico , Curva ROC , Síndrome de Dificultad Respiratoria/diagnóstico , Sepsis/complicaciones , Sepsis/diagnóstico
20.
Front Immunol ; 12: 742990, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34970255

RESUMEN

Background: Human parvovirus B19 (B19) can cause acute hepatitis and is attributed to the high mortality of alcoholic hepatitis (AH). B19 infection is generally self-healing in previously healthy people, but it can cause fatal effects in some high-risk groups and increase its virulence and infectivity. Disseminated B19 infection-induced multiple organ dysfunction syndrome (MODS) in patients with AH has not been reported yet. Here, we described B19 viremia in an adult patient with AH accompanied by hemolytic anemia (HA), leading to disseminated infection and secondary MODS, as well as self-limiting B19 infections in seven nurses caring for him. Meanwhile, we reviewed the literature on AH and B19 infection. Case Presentation: A 43-year-old male patient with AH accompanied by HA was transferred to the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, on March 31, 2021. After supportive treatment, his transaminase and bilirubin levels were reduced, but his anemia worsened. He received a red blood cell (RBC) infusion on April 9 for hemoglobin (Hb) lower than 6 g/dl. On April 13, he suddenly had a high fever. Under empirical anti-infection, his high fever dropped and maintained at a low fever level; however, his anemia worsened. On April 25, he was transferred to the medical intensive care unit (MICU) due to severe pneumonia, acute respiratory distress syndrome (ARDS), acute aplastic crisis (AAC), and hemophagocytic syndrome (HPS), which were subsequently confirmed to be related to B19 infection. After methylprednisolone, intravenous immunoglobulin (IVIG), empirical anti-infection, and supportive treatment, the lung infection improved, but hematopoietic and liver abnormalities aggravated, and systemic B19 infection occurred. Finally, the patient developed a refractory arrhythmia, heart failure, and shock and was referred to a local hospital by his family on May 8, 2021. Unfortunately, he died the next day. Fourteen days after he was transferred to MICU, seven nurses caring for him in his first two days in the MICU developed self-limiting erythema infectiosum (EI). Conclusions: B19 infection is self-limiting in healthy people, with low virulence and infectivity; however, in AH patients with HA, it can lead to fatal consequences and high contagion.


Asunto(s)
Anemia Hemolítica/inmunología , Hepatitis Alcohólica/inmunología , Insuficiencia Multiorgánica/inmunología , Infecciones por Parvoviridae/inmunología , Parvovirus B19 Humano/inmunología , Adulto , Hepatitis Alcohólica/diagnóstico , Humanos , Masculino , Insuficiencia Multiorgánica/diagnóstico , Infecciones por Parvoviridae/diagnóstico
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