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1.
J Cardiothorac Surg ; 19(1): 392, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937772

RESUMO

BACKGROUND: Currently, the differentiation between benign and malignant cystic pulmonary nodules poses a significant challenge for clinicians. The objective of this retrospective study was to construct a predictive model for determining the likelihood of malignancy in patients with cystic pulmonary nodules. METHODS: The current study involved 129 patients diagnosed with cystic pulmonary nodules between January 2017 and June 2023 at the Neijiang First People's Hospital. The study gathered the clinical data, preoperative imaging features of chest CT, and postoperative histopathological results for both cohorts. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors, from which a prediction model and nomogram were developed. In addition, The model's performance was assessed through receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). RESULTS: A cohort of 129 patients presenting with cystic pulmonary nodules, consisting of 92 malignant and 37 benign lesions, was examined. Logistic data analysis identified a cystic airspace with a mural nodule, spiculation, mural morphology, and the number of cystic cavities as significant independent predictors for discriminating between benign and malignant cystic lung nodules. The nomogram prediction model demonstrated a high level of predictive accuracy, as evidenced by an area under the ROC curve (AUC) of 0.874 (95% CI: 0.804-0.944). Furthermore, the calibration curve of the model displayed satisfactory calibration. DCA proved that the prediction model was useful for clinical application. CONCLUSION: In summary, the risk prediction model for benign and malignant cystic pulmonary nodules has the potential to assist clinicians in the diagnosis of such nodules and enhance clinical decision-making processes.


Assuntos
Neoplasias Pulmonares , Nomogramas , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Diagnóstico Diferencial , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Idoso , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Curva ROC , Adulto , Radiômica
2.
Ital J Pediatr ; 50(1): 121, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38915054

RESUMO

BACKGROUND: Townes-Brocks syndrome (TBS) is a rare genetic disorder characterized by imperforate anus, dysplastic ears, thumb malformations, and other abnormalities. Previous studies have revealed that mutations in the SALL1 gene can disrupt normal development, resulting in the characteristic features of Townes-Brocks syndrome. Spalt-like transcription factors (SALLs) are highly conserved proteins that play important roles in various cellular processes, including embryonic development, cell differentiation, and cell survival. Over 400 different variants or mutations have been reported in the SALL1 gene in individuals with TBS. Most of these variants lead to the formation of premature termination codons (PTCs), also known as nonsense mutations. The majority of these PTCs occur in a specific region of the SALL1 gene called the "hotspot region", which is particularly susceptible to mutation. METHODS: In this study, we conducted whole-exome sequencing on a three-generation Chinese family with anorectal malformations. RESULTS: We identified a novel heterozygous mutation (chr16:51175376:c.757 C > T p.Gln253*) in the SALL1 gene. Molecular analysis revealed a heterozygous C to T transition at nucleotide position 757 in exon 2 of the SALL1 (NM_002968) gene. This mutation is predicted to result in the substitution of the Gln253 codon with a premature stop codon (p.Gln253*). The glutamine-rich domain forms a long alpha helix, enabling the mutant protein to interact with the wild-type SALL1 protein. This interaction may result in steric hindrance effects on the wild-type SALL1 protein. CONCLUSIONS: Our findings have expanded the mutation database of the SALL1 gene, which is significant for genetic counseling and clinical surveillance in the affected family. Furthermore, our study enhances the understanding of Townes-Brocks syndrome and has the potential to improve its diagnosis and treatment.


Assuntos
Anormalidades Múltiplas , Anus Imperfurado , Linhagem , Fatores de Transcrição , Humanos , Fatores de Transcrição/genética , Anormalidades Múltiplas/genética , Anus Imperfurado/genética , Feminino , Masculino , China , Mutação , Doenças Raras/genética , Malformações Anorretais/genética , Povo Asiático/genética , População do Leste Asiático , Perda Auditiva Neurossensorial , Polegar/anormalidades
3.
PLoS One ; 19(6): e0305980, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38917102

RESUMO

BACKGROUND: Post-induction hypotension (PIH) often occurs during general anesthesia induction. This study aimed to investigate blood catecholamine levels during induction of general anesthesia in patients with PIH undergoing laparoscopic cholecystectomy. METHODS: This prospective study included 557 adult patients who underwent laparoscopic cholecystectomy under general anesthesia. PIH was defined as a greater than 20% decrease in systolic blood pressure from the pre-induction value, a systolic arterial pressure of less than 90 mmHg, or both. Plasma concentrations of epinephrine and norepinephrine during the induction of general anesthesia were determined using enzyme-linked immunosorbent assay. Multivariate logistic regression analysis evaluated the association between the clinical factors and PIH. RESULTS: Of the 557 patients, 390 had PIH, and the remaining 167 were allocated to the non-PIH group. Changes in blood adrenaline, noradrenaline levels, or both were more pronounced in the PIH than in the non-PIH group (p<0.05). Age, body mass index, a history of hypertension, preoperative systolic blood pressure, and propofol or sufentanil dose were independent predictors of PIH. CONCLUSION: The changes of blood catecholamines in patients with more stable hemodynamics during the induction of general anesthesia are smaller than that in patients with post-induction hypotension. TRIAL REGISTRATION: ChiCTR2200055549, 12/01/2022.


Assuntos
Anestesia Geral , Catecolaminas , Colecistectomia Laparoscópica , Hipotensão , Humanos , Colecistectomia Laparoscópica/efeitos adversos , Masculino , Feminino , Anestesia Geral/efeitos adversos , Pessoa de Meia-Idade , Estudos Prospectivos , Hipotensão/sangue , Hipotensão/etiologia , Adulto , Catecolaminas/sangue , Pressão Sanguínea , Idoso , Norepinefrina/sangue , Epinefrina/sangue
4.
Ann Med ; 56(1): 2362871, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38902986

RESUMO

The lung is an important site of extramedullary platelet formation, and megakaryocytes in the lung participate in immune responses in addition to platelet production. In acute lung injury and chronic lung injury, megakaryocytes and platelets play a promoting or protective role through different mechanisms. The authors reviewed the role of megakaryocytes and platelets in common clinical lung injuries with different course of disease and different pathogenic factors in order to provide new thinking for the diagnosis and treatment of lung injuries.


What is the context?Platelets are specialized non-nucleated blood cells produced by cytoplasmic lysis of megakaryocytes.HSCs differentiate into granular mature megakaryocytes and produce platelets.Lung is a reservoir of megakaryocytes and a site where platelets are produced in addition to bone marrow and spleen.Lung injury can be divided into acute lung injury and chronic lung injury, and characterized by different pathogenesis.Platelets and megakaryocytes are involved in hemostasis and regulation of the body 's inflammatory response.The disease state of the lung affects the functions of megakaryocytes and platelets.The role of megakaryocytes and platelets in acute and chronic lung injury is poorly studied.What is new?Platelets in the lung are derived not only from the spleen and bone marrow, but also from megakaryocytes in the pulmonary circulation. In this study, we demonstrated that pulmonary megakaryocytes not only produce platelets to play a hemostatic role in lung injury, but also participate in inflammation and immune response with platelets to promote the process of lung injury or play a protective role.Therefore, it was suggested in our analysis that targeting lung megakaryocytes and platelets is currently a new direction for the treatment of a variety of lung injuries.What is the impact?This review intends to explain the relationship between megakaryocytes, platelets and many types of lung injury from the mechanism of platelet production in the lung, and make a prospect in the new progress in the diagnosis and treatment of lung injury.


Assuntos
Lesão Pulmonar Aguda , Plaquetas , Megacariócitos , Humanos , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar , Pulmão/patologia , Animais , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/imunologia
5.
BMC Psychiatry ; 24(1): 459, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898451

RESUMO

BACKGROUND: Tinnitus affects approximately 740 million adults globally, involving hearing, emotion, and sleep systems. However, studies using polysomnography and pure-tone audiometry (PTA) are limited. We aimed to assess the correlation between tinnitus and hearing, sleep quality, characteristics, and depression using polysomnography and PTA. METHODS: In this cross-sectional study, we divided participants into tinnitus and non-tinnitus groups. We included 100 outpatients (65 with tinnitus, 35 without) from a medical center in Taiwan, who underwent polysomnography and completed rating scales including the Patient Health Questionnaire-9 (PHQ-9), Chinese version of the Pittsburgh Sleep Quality Index (PSQI), and Chinese-Mandarin version of the Tinnitus Handicap Inventory (THI-CM). We analyzed correlations, conducted group comparisons, assessed factors related to THI-CM scores, constructed ROC curves to predict depression in the tinnitus group, and performed multinomial and logistic regression to explore associations. RESULTS: Descriptive statistics identified a cohort with mean age 53.9 ± 12.80 years, 63% exhibited PHQ-9 scores ≥ 10, and 66% had Apnea-Hypopnea Index (AHI) > 5. The ratio of rapid eye movement and deep sleep to stage 1 + 2 sleep was relatively low and non-significant. Likewise, leg movements was higher in the tinnitus group but not statistically significant. In the tinnitus group, 63.08% had depression, and 81.54% had AHI > 5. Univariate logistic regression linked tinnitus to AHI > 5 (Odds ratio (OR) 2.67, p = 0.026) and male sex (OR 2.49, p = 0.034). A moderate positive correlation was found between the THI-CM score and PHQ-9 score (rs = 0.50, p < 0.001). Further adjustment for obstructive sleep apnea showed associations between PHQ-9 (total score) or depression and THI-CM Grade 3-5 (OR = 1.28; OR = 8.68). Single- and multifactor regression analyses highlighted significant associations of PSQI scores > 13 (OR 7.06, p = 0.018) and THI-CM scores > 47 (OR 7.43, p = 0.002) with depression. CONCLUSIONS: Our study recruited tinnitus participants with slight or mild hearing loss and mild tinnitus handicap. Depression was identified as a predominant factor in tinnitus-related handicap. The mild tinnitus handicap in tinnitus participants may explain the lack of significant differences in depression, sleep quality, and polysomnographic sleep characteristics between tinnitus and non-tinnitus groups. Further extensive and prospective studies are needed to elucidate the complex links among depression, sleep, and tinnitus.


Assuntos
Audiometria de Tons Puros , Polissonografia , Qualidade do Sono , Zumbido , Humanos , Masculino , Feminino , Zumbido/complicações , Zumbido/psicologia , Zumbido/diagnóstico , Pessoa de Meia-Idade , Estudos Transversais , Adulto , Idoso , Taiwan , Depressão/complicações , Depressão/diagnóstico
6.
Trials ; 25(1): 405, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907276

RESUMO

BACKGROUND: The inter-reviewer reliability of the risk of bias (RoB) assessment lacked agreement in previous studies. It is important to analyse these disagreements to improve the repeatability of RoB assessment. The objective of the study was to evaluate the frequency and reasons for disagreements in RoB assessments for randomised controlled trials (RCTs) that were included in multiple Cochrane reviews in the field of hypertension. METHODS: A cross-sectional study was employed. We retrieved any RCTs that had been included in multiple Cochrane reviews in the field of hypertension from ARCHIE. The results of the RoB assessments were extracted, and the distributions of agreements and possible reasons for disagreement were analyzed. RESULTS: Twenty-six Cochrane reviews were included in this study. A total of 78 RCTs appeared in more than one Cochrane review. The level of agreement ranged from domain to domain. "Blinding of outcome assessment" showed a reasonably high level of agreement (94.9%), while "incomplete outcome data", "selective outcome reporting" and "other sources of bias" showed moderate levels of agreement (74.6%, 79.2% and 75.6%, respectively). However, the domains of "allocation concealment", "random sequence generation" and "blinding of participants and personnel" showed low levels of agreement (24.4%, 23.5%, and 47.4%, respectively). In the domains of "allocation concealment" and "blinding of participants and personnel", the agreement group had higher proportion of publication year ≤ 1996 than the disagreement group (P = 0.008 and P < 0.001, respectively). In the "blinding of participants and personnel", the impact factor was higher in the agreement group (P < 0.001). By analyzing the support text, we found that the most likely reason for disagreement was extracting different information from the same RCT. CONCLUSION: For Cochrane reviews in the field of hypertension using the 2011 version of the RoB tool, there was a large disagreement in the RoB assessment. It is suggested that the results of RoB assessments in systematic reviews that used the 2011 version of the RoB tool need to be interpreted with caution. More accurate information from RCTs needs to be collected when we synthesize clinical evidence.


Assuntos
Viés , Hipertensão , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Hipertensão/diagnóstico , Estudos Transversais , Literatura de Revisão como Assunto , Projetos de Pesquisa , Medição de Risco , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Resultado do Tratamento , Fatores de Risco
7.
Diagn Microbiol Infect Dis ; 110(1): 116400, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38909426

RESUMO

Drug resistance surveillance is a major integral part of malaria control programs. Molecular methods play a pivotal role in drug resistance detection and related molecular research. This study aimed to develop a rapid and accurate detection method for drug resistance of Plasmodium falciparum (P. falciparum). A quantitative real-time PCR (qPCR) assay has been developed that identifies the mutation at locus A256T in the P.falciparum multi-drug resistance(pfmdr1) gene producing amino acid change at position 86. The results of 198 samples detected by qPCR were consistent with nested PCR and sequencing, giving an accuracy of 94.3%. The sensitivity, specificity, positive and negative predictive value of qPCR were 85.7%, 97.6%, 90.0% and 96.4%, respectively. The results of qPCR are basically consistent with the nested PCR, which is expected to replace the nested PCR as a new molecular biological method for drug resistance detection, providing reliable technical support for global malaria prevention and control.

8.
Support Care Cancer ; 32(7): 409, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834818

RESUMO

PURPOSE: To explore the resources, parents with cancer and their partners draw upon to sustain their family resilience through the cancer experience. METHODS: Fifteen participants who were parents of children aged 8 to 25 years completed phone, audio-recorded, and semi-structured interviews. Of these participants, 11 were parents diagnosed with cancer, and four were partners of a parent diagnosed with cancer. Interview questions aimed to increase understanding about how families communicate, connect, and face challenges from the cancer experience. Interview data was analysed using inductive thematic analysis to provide scope to generate themes from parent's experiences rather than to test pre-existing frameworks. RESULTS: The thematic analysis of interview transcripts generated three key themes related to family resilience: (1) adaptability to changes in roles and routines, (2) open communication within the family, and (3) accepting support from others. CONCLUSION: This study found that parents' ability to use personal resources when faced with significant challenges helped to improve the resilience of parents' family system. Further research is needed to understand the factors that influence family resilience when a parent is diagnosed with cancer. Implications for the development of targeted interventions that provide support to not only the patient, but their whole family system will be discussed.


Assuntos
Adaptação Psicológica , Neoplasias , Pais , Resiliência Psicológica , Humanos , Feminino , Masculino , Neoplasias/psicologia , Criança , Adulto , Adolescente , Pais/psicologia , Adulto Jovem , Pessoa de Meia-Idade , Apoio Social , Comunicação , Entrevistas como Assunto , Pesquisa Qualitativa
10.
FEBS Lett ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886124

RESUMO

The multidrug resistance-associated protein (MRP) ABCC4 facilitates substrate transport across the cytoplasmic membrane, crucial for normal physiology and mediating multidrug resistance in tumor cells. Despite intensive studies on MRPs, ABCC4's transport mechanism remains incompletely understood. In this study, we unveiled an inward-open conformation with an ATP bound to degenerate NBD1. Additionally, we captured the structure with both ATP and substrate co-bound in the inward-open state. Our findings uncover the asymmetric ATP binding in ABCC4 and provide insights into substrate binding and transport mechanisms. ATP binding to NBD1 is parallel to substrate binding to ABCC4, and is a prerequisite for ATP-bound NBD2-induced global conformational changes. Our findings shed new light on targeting ABCC4 in combination with anticancer therapy.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38874521

RESUMO

AIMS: Mitochondrial dynamics in alveolar macrophages (AMs) are associated with sepsis-induced acute lung injury (ALI). In this study, we aimed to investigate whether changes in mitochondrial dynamics could alter the polarization of AMs in sepsis-induced ALI and to explore the regulatory mechanism of mitochondrial dynamics by focusing on SIRT3-induced optic atrophy protein 1 (OPA1) deacetylation. RESULTS: The AMs of sepsis-induced ALI showed imbalanced mitochondrial dynamics and polarization to the M1 macrophage phenotype. In sepsis, SIRT3 overexpression promotes mitochondrial dynamic equilibrium in AMs. However, 3TYP-specific inhibition of SIRT3 increased the mitochondrial dynamic imbalance and pro-inflammatory polarization of AMs and further aggravated sepsis-induced ALI. OPA1 is directly bound to and deacetylated by SIRT3 in AMs. In AMs of sepsis-induced ALI, SIRT3 protein expression was decreased and OPA1 acetylation was increased. OPA1 acetylation at the lysine 792 amino acid residue (OPA1-K792) promotes self-cleavage and is associated with an imbalance in mitochondrial dynamics. However, decreased acetylation of OPA1-K792 reversed the pro-inflammatory polarization of AMs and protected the barrier function of alveolar epithelial cells in sepsis-induced ALI. INNOVATION: Our study revealed for the first time the regulation of mitochondrial dynamics and AMs polarization by SIRT3-mediated deacetylation of OPA1 in sepsis-induced ALI, which may serve as an intervention target for precision therapy of the disease. CONCLUSIONS: Our data suggest that imbalanced mitochondrial dynamics promote pro-inflammatory polarization of AMs in sepsis-induced ALI, and that deacetylation of OPA1 mediated by SIRT3 improves mitochondrial dynamic equilibrium, thereby ameliorating lung injury.

12.
J Proteomics ; 303: 105202, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38797434

RESUMO

Deficiency in fragile X mental retardation 1 (Fmr1) leads to loss of its encoded protein FMRP and causes fragile X syndrome (FXS) by dysregulating its target gene expression in an age-related fashion. Using comparative proteomic analysis, this study identified 105 differentially expressed proteins (DEPs) in the hippocampus of postnatal day 7 (P7) Fmr1-/y mice and 306 DEPs of P90 Fmr1-/y mice. We found that most DEPs in P90 hippocampus were not changed in P7 hippocampus upon FMRP absence, and some P90 DEPs exhibited diverse proteophenotypes with abnormal expression of protein isoform or allele variants. Bioinformatic analyses showed that the P7 DEPs were mainly enriched in fatty acid metabolism and oxidoreductase activity and nutrient responses; whereas the P90 PEPs (especially down-regulated DEPs) were primarily enriched in postsynaptic density (PSD), neuronal projection development and synaptic plasticity. Interestingly, 25 of 30 down-regulated PSD proteins present in the most enriched protein to protein interaction network, and 6 of them (ANK3, ATP2B2, DST, GRIN1, SHANK2 and SYNGAP1) are both FMRP targets and autism candidates. Therefore, this study suggests age-dependent alterations in hippocampal proteomes upon loss of FMRP that may be associated with the pathogenesis of FXS and its related disorders. SIGNIFICANCE: It is well known that loss of FMRP resulted from Fmr1 deficiency leads to fragile X syndrome (FXS), a common neurodevelopmental disorder accompanied by intellectual disability and autism spectrum disorder (ASD). FMRP exhibits distinctly spatiotemporal patterns in the hippocampus between early development and adulthood, which lead to distinct dysregulations of gene expression upon loss of FMRP at the two age stages potentially linked to age-related phenotypes. Therefore, comparison of hippocampal proteomes between infancy and adulthood is valuable to provide insights into the early causations and adult-dependent consequences for FXS and ASD. Using a comparative proteomic analysis, this study identified 105 and 306 differentially expressed proteins (DEPs) in the hippocampi of postnatal day 7 (P7) and P90 Fmr1-/y mice, respectively. Few overlapping DEPs were identified between P7 and P90 stages, and the P7 DEPs were mainly enriched in the regulation of fatty acid metabolism and oxidoreduction, whereas the P90 DEPs were preferentially enriched in the regulation of synaptic formation and plasticity. Particularly, the up-regulated P90 proteins are primarily involved in immune responses and neurodegeneration, and the down-regulated P90 proteins are associated with postsynaptic density, neuron projection and synaptic plasticity. Our findings suggest that distinctly changed proteins in FMRP-absence hippocampus between infancy and adulthood may contribute to age-dependent pathogenesis of FXS and ASD.


Assuntos
Proteína do X Frágil da Deficiência Intelectual , Síndrome do Cromossomo X Frágil , Hipocampo , Proteoma , Animais , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Proteína do X Frágil da Deficiência Intelectual/genética , Hipocampo/metabolismo , Camundongos , Proteoma/metabolismo , Proteoma/análise , Síndrome do Cromossomo X Frágil/metabolismo , Densidade Pós-Sináptica/metabolismo , Camundongos Knockout , Proteômica , Masculino , Envelhecimento/metabolismo , Plasticidade Neuronal
13.
Front Oncol ; 14: 1376496, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741782

RESUMO

FOXK2, a member of the Forkhead box K (FOXK) transcription factor family, is widely expressed in various tissues and organs throughout the body. FOXK2 plays crucial roles in cell proliferation, differentiation, autophagy, de novo nucleotide biosynthesis, DNA damage response, and aerobic glycolysis. Although FOXK2 is recognized as an oncogene in colorectal cancer and hepatocellular carcinoma, it acts as a tumor suppressor in breast cancer, cervical cancer, and non-small cell lung cancer (NSCLC). This review provides an overview of the recent progress in understanding the regulatory mechanisms of FOXK2 and its downstream targets, highlights the significant impact of FOXK2 dysregulation on cancer etiology, and discusses the potential of targeting FOXK2 for cancer treatment.

14.
J Nanobiotechnology ; 22(1): 221, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724958

RESUMO

Intra-articular drugs used to treat osteoarthritis (OA) often suffer from poor pharmacokinetics and stability. Nano-platforms as drug delivery systems for drug delivery are promising for OA therapy. In this study, we reported an M1 macrophage-targeted delivery system Bai@FA-UIO-66-NH2 based on folic acid (FA) -modified metal-organic framework (MOF) loaded with baicalin (Bai) as antioxidant agent for OA therapy. With outstanding biocompatibility and high drug loading efficiency, Bai@FA-UIO-66-NH2 could be specifically uptaken by LPS-induced macrophages to serve as a potent ROS scavenger, gradually releasing Bai at the subcellular level to reduce ROS production, modulate macrophage polarization to M2, leading to alleviation of synovial inflammation in OA joints. The synergistic effect of Bai@FA-UIO-66-NH2 on macrophage polarization and ROS scavenging significantly improved the therapeutic efficacy of OA, which may provide a new insight into the design of OA precision therapy.


Assuntos
Flavonoides , Macrófagos , Estruturas Metalorgânicas , Osteoartrite , Espécies Reativas de Oxigênio , Estruturas Metalorgânicas/química , Osteoartrite/tratamento farmacológico , Animais , Flavonoides/farmacologia , Flavonoides/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Células RAW 264.7 , Antioxidantes/farmacologia , Antioxidantes/química , Sistemas de Liberação de Medicamentos/métodos , Ácido Fólico/química , Masculino , Ratos , Lipopolissacarídeos/farmacologia , Ratos Sprague-Dawley
15.
Dig Liver Dis ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38744557

RESUMO

OBJECTIVES: This study presents a novel computer-aided diagnosis (CADx) designed for optically diagnosing colorectal polyps using white light imaging (WLI).We aimed to evaluate the effectiveness of the CADx and its auxiliary role among endoscopists with different levels of expertise. METHODS: We collected 2,324 neoplastic and 3,735 nonneoplastic polyp WLI images for model training, and 838 colorectal polyp images from 740 patients for model validation. We compared the diagnostic accuracy of the CADx with that of 15 endoscopists under WLI and narrow band imaging (NBI). The auxiliary benefits of CADx for endoscopists of different experience levels and for identifying different types of colorectal polyps was also evaluated. RESULTS: The CADx demonstrated an optical diagnostic accuracy of 84.49%, showing considerable superiority over all endoscopists, irrespective of whether WLI or NBI was used (P < 0.001). Assistance from the CADx significantly improved the diagnostic accuracy of the endoscopists from 68.84% to 77.49% (P = 0.001), with the most significant impact observed among novice endoscopists. Notably, novices using CADx-assisted WLI outperform junior and expert endoscopists without such assistance. CONCLUSIONS: The CADx demonstrated a crucial role in substantially enhancing the precision of optical diagnosis for colorectal polyps under WLI and showed the greatest auxiliary benefits for novice endoscopists.

17.
Heliyon ; 10(10): e31202, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38803953

RESUMO

Background: Esophageal cancer (EC) is a prevalent malignancy with heterogeneous outcomes. This study explores the significance of anoikis-related long non-coding RNAs (lncRNAs) in EC, aiming to unravel their molecular roles and clinical implications. Methods: Transcriptome and clinical data were obtained from TCGA database for EC samples. We identified anoikis-related genes and lncRNAs by Pearson correlation analysis. The risk score model hinged on prognostic lncRNAs filtered from multiple steps. Risk scores were calculated using the derived formula, and categorized patients into low- and high-risk groups. Model robustness was assessed through Kaplan-Meier (KM) survival analysis and Receiver Operating Characteristic (ROC) curve, with clinical utility achieved via a constructed nomogram. We also explored the interplay between the risk score and immune cell infiltration, and investigated drug sensitivity. Results: We identified 2365 anoikis-related lncRNAs through co-expression analysis, including 1415 significant lncRNAs differentially expressed between normal and tumor samples. A risk score model was constructed from ten prognostic lncRNAs. The risk score model effectively stratified patients based on the median score, and its predictive capacity was validated through KM survival, ROC curve analyses, and the external GSE53622 dataset. The nomogram provided a practical tool for individualized prognosis evaluation. We unveiled significant correlations between specific immune cell subsets and the risk score. Eosinophils and common lymphoid progenitors exhibited positive associations, while endothelial cells and myeloid dendritic cells showed negative correlations. Drug sensitivity analysis revealed potential sensitive drugs for EC treatment that aligned with the risk subgroups. Conclusion: This study established an anoikis-related lncRNAs risk score model that may predict the prognosis, immune infiltration, and drug sensitivity in EC, in hope of facilitating tailored patient management.

18.
Neuroimage ; 294: 120640, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38719154

RESUMO

Attentional control, guided by top-down processes, enables selective focus on pertinent information, while habituation, influenced by bottom-up factors and prior experiences, shapes cognitive responses by emphasizing stimulus relevance. These two fundamental processes collaborate to regulate cognitive behavior, with the prefrontal cortex and its subregions playing a pivotal role. Nevertheless, the intricate neural mechanisms underlying the interaction between attentional control and habituation are still a subject of ongoing exploration. To our knowledge, there is a dearth of comprehensive studies on the functional connectivity between subsystems within the prefrontal cortex during attentional control processes in both primates and humans. Utilizing stereo-electroencephalogram (SEEG) recordings during the Stroop task, we observed top-down dominance effects and corresponding connectivity patterns among the orbitofrontal cortex (OFC), the middle frontal gyrus (MFG), and the inferior frontal gyrus (IFG) during heightened attentional control. These findings highlighting the involvement of OFC in habituation through top-down attention. Our study unveils unique connectivity profiles, shedding light on the neural interplay between top-down and bottom-up attentional control processes, shaping goal-directed attention.


Assuntos
Atenção , Eletroencefalografia , Habituação Psicofisiológica , Córtex Pré-Frontal , Humanos , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Atenção/fisiologia , Masculino , Feminino , Eletroencefalografia/métodos , Habituação Psicofisiológica/fisiologia , Adulto , Adulto Jovem , Teste de Stroop
19.
Phytomedicine ; 129: 155591, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38692075

RESUMO

BACKGROUND: Acute lung injury (ALI) is a continuum of lung changes caused by multiple lung injuries, characterized by a syndrome of uncontrolled systemic inflammation that often leads to significant morbidity and death. Anti-inflammatory is one of its treatment methods, but there is no safe and available drug therapy. Syringic acid (SA) is a natural organic compound commonly found in a variety of plants, especially in certain woody plants and fruits. In modern pharmacological studies, SA has anti-inflammatory effects and therefore may be a potentially safe and available compound for the treatment of acute lung injury. PURPOSE: This study attempts to reveal the protective mechanism of SA against ALI by affecting the polarization of macrophages and the activation of NF-κB signaling pathway. Trying to find a safer and more effective drug therapy for clinical use. METHODS: We constructed the ALI model using C57BL/6 mice by intratracheal instillation of LPS (10 mg/kg). Histological analysis was performed with hematoxylin and eosin (H&E). The wet-dry ratio of the whole lung was measured to evaluate pulmonary edema. The effect of SA on macrophage M1-type was detected by flow cytometry. BCA protein quantification method was used to determine the total protein concentration in bronchoalveolar lavage fluid (BALF). The levels of Interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α in BALF were determined by the ELISA kits, and RT-qPCR was used to detect the expression levels of IL-6, IL-1ß and TNF-α mRNA of lung tissue. Western blot was used to detect the expression levels of iNOS and COX-2 and the phosphorylation of p65 and IκBα in the NF-κB pathway in lung tissue. In vitro experiments were conducted with RAW267.4 cell inflammation model induced by 100 ng/ml LPS and A549 cell inflammation model induced by 10 µg/ml LPS. The effects of SA on M1-type and M2-type macrophages of RAW267.4 macrophages induced by LPS were detected by flow cytometry. The toxicity of compound SA to A549 cells was detected by MTT method which to determine the safe dose of SA. The expressions of COX-2 and the phosphorylation of p65 and IκBα protein in NF-κB pathway were detected by Western blot. RESULTS: We found that the pre-treatment of SA significantly reduced the degree of lung injury, and the infiltration of neutrophils in the lung interstitium and alveolar space of the lung. The formation of transparent membrane in lung tissue and thickening of alveolar septum were significantly reduced compared with the model group, and the wet-dry ratio of the lung was also reduced. ELISA and RT-qPCR results showed that SA could significantly inhibit the production of IL-6, IL-1ß, TNF-α. At the same time, SA could significantly inhibit the expression of iNOS and COX-2 proteins, and could inhibit the phosphorylation of p65 and IκBα proteins. in a dose-dependent manner. In vitro experiments, we found that flow cytometry showed that SA could significantly inhibit the polarization of macrophages from M0 type macrophages to M1-type macrophages, while SA could promote the polarization of M1-type macrophages to M2-type macrophages. The results of MTT assay showed that SA had no obvious cytotoxicity to A549 cells when the concentration was not higher than 80 µM, while LPS could promote the proliferation of A549 cells. In the study of anti-inflammatory effect, SA can significantly inhibit the expression of COX-2 and the phosphorylation of p65 and IκBα proteins in LPS-induced A549 cells. CONCLUSION: SA has possessed a crucial anti-ALI role in LPS-induced mice. The mechanism was elucidated, suggesting that the inhibition of macrophage polarization to M1-type and the promotion of macrophage polarization to M2-type, as well as the inhibition of NF-κB pathway by SA may be the reasons for its anti-ALI. This finding provides important molecular evidence for the further application of SA in the clinical treatment of ALI.


Assuntos
Lesão Pulmonar Aguda , Ácido Gálico , Lipopolissacarídeos , Macrófagos , Camundongos Endogâmicos C57BL , NF-kappa B , Animais , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Camundongos , Ácido Gálico/farmacologia , Ácido Gálico/análogos & derivados , Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , Masculino , Transdução de Sinais/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Pulmão/efeitos dos fármacos , Pulmão/patologia , Células RAW 264.7 , Interleucina-1beta/metabolismo , Líquido da Lavagem Broncoalveolar , Óxido Nítrico Sintase Tipo II/metabolismo , Interleucina-6/metabolismo
20.
Membranes (Basel) ; 14(5)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38786943

RESUMO

The membrane biofilm reactor (MBfR) is a novel wastewater treatment technology, garnering attention due to its high gas utilization rate and effective pollutant removal capability. This paper outlines the working mechanism, advantages, and disadvantages of MBfR, and the denitrification pathways, assessing the efficacy of MBfR in removing oxidized pollutants (sulfate (SO4-), perchlorate (ClO4-)), heavy metal ions (chromates (Cr(VI)), selenates (Se(VI))), and organic pollutants (tetracycline (TC), p-chloronitrobenzene (p-CNB)), and delves into the role of related microorganisms. Specifically, through the addition of nitrates (NO3-), this paper analyzes its impact on the removal efficiency of other pollutants and explores the changes in microbial communities. The results of the study show that NO3- inhibits the removal of other pollutants (oxidizing pollutants, heavy metal ions and organic pollutants), etc., in the simultaneous removal of multiple pollutants by MBfR.

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