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ABSTRACT: This study aims to explore the value of real-time strain elastography (RTE) and contrast-enhanced ultrasonography (CEUS) in the diagnosis of breast BI-RADS 4 lesions. It collected 85 cases (totaling 85 lesions) diagnosed with breast BI-RADS 4 through routine ultrasound from October 2020 to December 2022 in Huangshan City People's Hospital. All lesions underwent RTE and CEUS examination before surgery, and the ImageJ software was used to measure the periphery of lesion images in the enhancement peak mode and grayscale mode to calculate the contrast-enhanced ultrasound area ratio. The diagnostic capabilities of single-modal and multimodal ultrasound examination for the malignancy of breast BI-RADS 4 lesions were compared using the receiver operating characteristic curve; the Spearman correlation analysis was adopted to evaluate the correlation between multimodal ultrasound and CEUS area ratio. As a result, among the 85 lesions, 51 were benign, and 34 were malignant. The areas under the curve (AUCs) of routine ultrasound (US), US + RTE, US + CEUS, and US + RTE + CEUS were 0.816, 0.928, 0.953, and 0.967, respectively, with the combined method showing a higher AUC than the single application. The AUC of the CEUS area ratio diagnosing breast lesions was 0.888. There was a strong positive correlation (r = 0.819, P < 0.001) between the diagnostic performance of US + RTE + CEUS and the CEUS area ratio. In conclusion, based on routine ultrasound, the combination of RTE and CEUS can further improve the differential diagnosis of benign and malignant lesions in breast BI-RADS 4.
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Neoplasias da Mama , Mama , Meios de Contraste , Técnicas de Imagem por Elasticidade , Ultrassonografia Mamária , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Ultrassonografia Mamária/métodos , Pessoa de Meia-Idade , Diagnóstico Diferencial , Adulto , Técnicas de Imagem por Elasticidade/métodos , Mama/diagnóstico por imagem , Imagem Multimodal/métodos , Idoso , Reprodutibilidade dos Testes , Adulto Jovem , Aumento da Imagem/métodosRESUMO
A new trifluoroacetylation reagent was developed by using inexpensive and readily available trifluoroacetic anhydride and N-phenyl-4-methylbenzenesulfonamide for the first time. The reaction of (het)aryl boronic acids with the new trifluoroacetylation reagent, N-phenyl-N-tosyltrifluoroacetamide, proceeded smoothly in the presence of a palladium catalyst to provide trifluoromethyl ketones in satisfactory to excellent yields. Various groups, including the synthetically useful functional groups Cl, TMS, and PhCO, were tolerated well under the current reaction conditions. This new trifluoroacetylation reagent can be used in the large-scale synthesis of trifluoromethyl ketones, even at a low palladium catalyst loading.
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A new radical difluoromethylation was developed by using inexpensive and readily available difluoroacetic anhydride and N-phenyl-4-methylbenzenesulfonamide for the first time. The reaction of arylboronic acids with the new difluoromethylation reagent, N-phenyl-N-tosyldifluoroacetamide, proceeded smoothly in the presence of palladium catalyst to provide difluoromethylarenes in satisfactory to excellent yields. The electronic property (electron-donating or electron-withdrawing) of the substituent linked to the aromatic ring did not considerably influence the reactivity of arylboronic acid. Various groups, including the synthetically useful functional groups Cl, CN, and NO2, were tolerated well under the current reaction conditions.
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Two efficient and convenient methods for the synthesis of 3-alkylideneoxindoles are described in this paper. The InCl3/TfOH-mediated tandem Knoevenagel condensation-deacylation sequence of various 2-oxindoles with 1,3-diones or acetoacetate furnished 3-alkylideneoxindoles in satisfactory to excellent yields (up to >99% yield). Employing the reaction system, the condensation of 2-oxindoles with ketones or aldehydes also proceeded smoothly to produce 3-alkylideneoxindoles. This protocol can be amenable to scale up. The effect of acids on this condensation reaction and intermolecular competition experiments were investigated to understand the aspect of the reaction.
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BACKGROUND: Fatigue is a debilitating symptom found in various chronic diseases and is associated with more severe symptoms and worse quality of life (QoL). However, this symptom has not been adequately addressed in chronic pancreatitis (CP), and there have been no studies on fatigue in patients with CP. METHODS: This cross-sectional study was conducted at the Changhai Hospital in Shanghai, China. Data on the patients' sociodemographic, disease, and therapeutic characteristics were collected. Fatigue was assessed using the Multidimensional Fatigue Inventory-20. QoL was assessed utilizing the European Organization for the Research and Treatment of Cancer of QoL questionnaire (EORTC-QLQ-C30). Sleep quality, anxiety and depression, and pain was assessed using Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and the Brief Pain Inventory, respectively. RESULTS: The prevalence of fatigue among Chinese patients with CP was 35.51 % (87/245). Multivariate analysis showed that steatorrhea (OR = 2.638, 95 % CI: 1.117-6.234), history of smoking (OR = 4.627, 95 % CI: 1.202-17.802), history of endoscopic treatment (OR = 0.419, 95 % CI: 0.185-0.950), depression (OR = 5.924, 95 % CI: 2.462-14.255), and sleep disorder (OR = 6.184, 95 % CI: 2.543-15.034) were influencing factors for the presence of fatigue. The scores for global health and all functional dimensions in the EORTC-QLQ-C30 significantly decreased, whereas the scores for all symptom dimensions significantly increased in patients with fatigue. CONCLUSIONS: This study indicated that Fatigue is a common symptom and has a negative impact on the QoL of patients with CP. Steatorrhea, smoking history, endoscopic treatment, depression, and sleep disorders were associated with fatigue.
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Pancreatite Crônica , Esteatorreia , Humanos , Estudos Transversais , Qualidade de Vida , Prevalência , China/epidemiologia , Fatores de Risco , Pancreatite Crônica/complicações , Pancreatite Crônica/epidemiologia , Fadiga/epidemiologia , Fadiga/etiologia , Dor , Inquéritos e QuestionáriosRESUMO
An efficient and convenient method for the synthesis of phenols and aliphatic alcohols is described in this paper. The oxidative hydroxylation reaction of various organoboron compounds proceeded smoothly by employing H2O2 as the oxidant and citric acid as the catalyst in water at room temperature to produce phenols and aliphatic alcohols in satisfactory to excellent yields (up to 99% yield). Various synthetically useful functional groups, such as halogen atom, cyano, and nitro groups, remain intact during the oxidative hydroxylation. The developed catalytic system also could accommodate phenylboronic pinacol ester and potassium phenyltrifluoroborate to give the target product good yields.
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The N-functionalized indole is a privileged structural framework in a wide range of bioactive molecules. The nucleophilic addition between indoles with vinylene carbonate proceeded smoothly in the presence of K2CO3 as the catalyst to produce novel indolyl-containing skeletons and 4-indolyl-1,3-dioxolanones in satisfactory to excellent yields (up to >97% yield). Various synthetically useful functional groups, such as halogen atoms, cyano, nitro, and methoxycarbonyl groups, remained intact during the regioselective N-H addition reactions. The developed catalytic system also could accommodate 2-naphthalenol to achieve the target O-H additive product in good yield.
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An efficient and convenient method for the synthesis of 2-trifluoromethyl benzimidazoles is described in this paper. The cyclization reaction of various o-phenylenediamines with hexafluoroacetylacetone proceeded smoothly in the presence of Cu2O as the catalyst to produce 2-trifluoromethyl benzimidazoles in satisfactory to excellent yields (up to >99% yield). The CF3 source, hexafluoroacetylacetone, acted not only as cyclization partner, but also acted as a ligand for the Cu catalyst. Various synthetically useful functional groups, such as halogen atoms, cyano, and methoxycarbonyl groups, remained intact during the cyclization reactions. The reaction mechanism was thoroughly investigated and was determined to involve a seven-membered cyclic diimine intermediate.
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IMPORTANCE: Mitochondrial antiviral signaling protein (MAVS) and stimulator of interferon (IFN) genes (STING) are key adaptor proteins required for innate immune responses to RNA and DNA virus infection. Here, we show that zebrafish transmembrane protein 47 (TMEM47) plays a critical role in regulating MAVS- and STING-triggered IFN production in a negative feedback manner. TMEM47 interacted with MAVS and STING for autophagic degradation, and ATG5 was essential for this process. These findings suggest the inhibitory function of TMEM47 on MAVS- and STING-mediated signaling responses during RNA and DNA virus infection.
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Infecções por Vírus de DNA , Imunidade Inata , Interferons , Infecções por Vírus de RNA , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Infecções por Vírus de DNA/imunologia , Infecções por Vírus de DNA/virologia , Interferons/antagonistas & inibidores , Interferons/biossíntese , Transdução de Sinais , Peixe-Zebra/imunologia , Peixe-Zebra/metabolismo , Peixe-Zebra/virologia , Infecções por Vírus de RNA/imunologia , Infecções por Vírus de RNA/virologia , Retroalimentação Fisiológica , Proteínas de Peixe-Zebra/imunologia , Proteínas de Peixe-Zebra/metabolismoRESUMO
OBJECTIVE: To evaluate the association between pulmonary hemorrhage and bronchopulmonary dysplasia (BPD) in very low birth weight infants (VLBWIs). METHODS: The study participants were all VLBW newborns admitted from January 1, 2019 to December 31, 2021. The BPD subjects finally included were VLBWIs who survived until the diagnosis was established. This study was divided into pulmonary hemorrhage group (PH group, n = 35) and non-pulmonary hemorrhage group (Non-PH group, n = 190). RESULTS: By univariate analysis it was found that premature rupture of membranes, tracheal intubation in the delivery room, duration of mechanical ventilation, course of invasive ventilation (≥3 courses), pulmonary surfactant (>1 dose), medically and surgically treated patent ductus arteriosus, grade III-IV RDS, early onset sepsis, BPD and moderate to severe BPD showed significant differences between groups (p < .05). By Multivariate analysis, pulmonary hemorrhage did not increase the risks of BPD and moderate to severe BPD (adjusted OR for BPD = 1.710, 95% CI 0.581-5.039; adjusted OR for moderate to severe BPD = 2.401, 95% CI 0.736-7.834). CONCLUSION: It suggests that pulmonary hemorrhage is not associated with the development of BPD and moderate to severe BPD in VLBWIs.
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Displasia Broncopulmonar , Permeabilidade do Canal Arterial , Lactente , Feminino , Recém-Nascido , Humanos , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/epidemiologia , Recém-Nascido de muito Baixo Peso , Peso ao Nascer , Respiração Artificial , Permeabilidade do Canal Arterial/complicações , Idade GestacionalRESUMO
BACKGROUND AND OBJECTIVES: In patients with colorectal cancer and clinically suspected para-aortic lymph node metastasis, the survival benefit of para-aortic lymphadenectomy is unknown. We conducted a meta-analysis and systematic review to investigate it. METHODS: PubMed, Web of Science, and EMBASE were searched until January 2000 to April 2022 to identify studies reporting overall survivals, complication rates, and hazard ratios of prognostic factors in patients with colorectal cancer undergoing para-aortic lymphadenectomy, and those data were pooled. RESULTS: Twenty retrospective studies (1021 patients undergoing para-aortic lymphadenectomy) met the inclusion criteria. Meta-analysis indicates that participants undergoing para-aortic lymphadenectomy were associated with 5-year survival benefit, compared to those not receiving para-aortic lymphadenectomy (odds ratio = 3.73, 95% confidence interval: 2.05-6.78), but there was no significant difference in complication rate (odds ratio = 0.97, 95% confidence interval: 0.46-2.08). Further analysis of para-aortic lymphadenectomy group showed that 5-year survival of the positive group with pathologically para-aortic lymph node metastasis was lower than that of the negative group (odds ratio = 0.19, 95% confidence interval: 0.11-0.31). Moreover, complete resection (odds ratio = 5.26, 95% confidence interval: 2.02-13.69), para-aortic lymph node metastasis (≤4) (hazard ratio = 1.88, 95% confidence interval: 0.97-3.62), and medium-high differentiation (hazard ratio = 2.98, 95% confidence interval: 1.48-5.99) were protective factors for survival. Preoperative extra-retroperitoneal metastasis was associated with poorer relapse-free survival (hazard ratio = 1.85, 95% confidence interval: 1.10-3.10). CONCLUSION: Para-aortic lymphadenectomy had promising clinical efficacy in prolonging survival rather than complication rate in patients with colorectal cancer and clinically diagnostic para-aortic lymph node metastasis. Further prospective studies should be performed. TRIAL REGISTRATION: PROSPERO: CRD42022379276.
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Neoplasias Colorretais , Excisão de Linfonodo , Humanos , Neoplasias Colorretais/cirurgia , Metástase Linfática , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Gastric cancer is the fifth most common cancer worldwide. With the development of immunotherapy, especially the application of immune checkpoint inhibitors (ICIs), the prognosis of advanced gastric cancer has improved. At present, ICIs combined with other therapies or dual ICI strategies in the treatment of advanced gastric cancer have shown clinical effectiveness and controllable safety. In addition, predictive biomarkers facilitate the precise selection of patients. Therefore, it is crucial to explore rational combinations and reliable predictive biomarkers for ICI therapy. This article reviews the recent advances in ICIs and relevant predictive biomarkers in the treatment of gastric cancer.
In recent years, with the application of immunotherapy, clinical efficacy in gastric cancer has been effectively improved. At present, it is encouraging that immunotherapy combined with chemotherapy has become the first choice for the treatment of patients with advanced gastric cancer. However, researchers remain committed to exploring the efficacy of immunotherapy in combination with various therapies. Equally important, the identification of biomarkers can facilitate the selection of patients suitable for immunotherapy. This article summarizes important immunotherapy clinical trials and discusses therapeutic combinations and biomarkers being explored.
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Inibidores de Checkpoint Imunológico , Neoplasias Gástricas , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Gástricas/terapia , Biomarcadores , Imunoterapia , PrognósticoRESUMO
Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson's disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson's disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson's disease. We then established a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson's disease.
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From insects to mammals, both innate and adaptive immune response are usually higher in females than in males, with the sex chromosome and hormonal differences considered the main reasons. Here, we report that zebrafish cyp19a1a (cytochrome P450, family 19, subfamily A, polypeptide 1a), an autosomal gene with female-biased expression, causes female fish to exhibit a lower antiviral response. First, we successfully constructed an infection model by intraperitoneal injection of spring viremia of carp virus (SVCV) into zebrafish (Danio rerio) and Carassius auratus herpesvirus (CaHV) in gibel carp (Carassius gibelio). Specifically, female fish were more vulnerable to viral infection than males, accompanied by a significantly weaker interferon (IFN) expression. After screening several candidates, cyp19a1a, which was highly expressed in female fish tissues, was selected for further analysis. The IFN expression and antiviral response were significantly higher in cyp19a1a-/- than in cyp19a1a+/+. Further investigation of the molecular mechanism revealed that Cyp19a1a targets mediator of IRF3 activation (MITA) for autophagic degradation. Interestingly, in the absence of MITA, Cyp19a1a alone could not elicit an autophagic response. Furthermore, the autophagy factor ATG14 (autophagy-related 14) was found interacted with Cyp19a1a to either promote or attenuate Cyp19a1a-mediated MITA degradation by either being overexpressed or knocked down, respectively. At the cellular level, both the normal and MITA-enhanced cellular antiviral responses were diminished by Cyp19a1a. These findings demonstrated a sex difference in the antiviral response based on a regulation mechanism controlled by a female-biased gene besides sex chromosome and hormonal differences, supplying the current understanding of sex differences in fish.
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Carpas , Doenças dos Peixes , Herpesviridae , Animais , Antivirais/farmacologia , Autofagia , Feminino , Imunidade Inata/genética , Masculino , Mamíferos , Peixe-Zebra/genéticaRESUMO
The postoperative survival time and quality of life of patients with colon adenocarcinoma (COAD) varies widely. In order to make accurate decisions after surgery, clinicians need to distinguish patients with different prognostic trends. However, we still lack effective methods to predict the prognosis of COAD patients. Accumulated evidences indicated that the inhibition of peroxisome proliferator-activated receptors (PPARs) and a portion of their target genes were associated with the development of COAD. Our study found that the expression of several PPAR pathway-related genes were linked to the prognosis of COAD patients. Therefore, we developed a scoring system (named PPAR-Riskscore) that can predict patients' outcomes. PPAR-Riskscore was constructed by univariate Cox regression based on the expression of 4 genes (NR1D1, ILK, TNFRSF1A, and REN) in tumor tissues. Compared to typical TNM grading systems, PPAR-Riskscore has better predictive accuracy and sensitivity. The reliability of the system was tested on six external validation datasets. Furthermore, PPAR-Riskscore was able to evaluate the immune cell infiltration and chemotherapy sensitivity of each tumor sample. We also combined PPAR-Riskscore and clinical features to create a nomogram with greater clinical utility. The nomogram can help clinicians make precise treatment decisions regarding the possible long-term survival of patients after surgery.
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In mammals, cyclic GMP-AMP synthase (cGAS) recognizes cytosolic dsDNA to induce the type I IFN response. However, the functional role of cGAS in the IFN response of fish remains unclear or controversial. In this study, we report that cGAS orthologs from crucian carp Carassius auratus (CacGAS) and grass carp Ctenopharyngodon idellus (CicGAS) target the dsRNA sensor retinoic acid-inducible gene I (RIG-I) for negative regulation of the IFN response. First, poly(deoxyadenylic-deoxythymidylic) acid-, polyinosinic-polycytidylic acid-, and spring viremia of carp virus-induced IFN responses were impaired by overexpression of CacGAS and CicGAS. Then, CacGAS and CicGAS interacted with CiRIG-I and CiMAVS and inhibited CiRIG-I- and CiMAVS-mediated IFN induction. Moreover, the K63-linked ubiquitination of CiRIG-I and the interaction between CiRIG-I and CiMAVS were attenuated by CacGAS and CicGAS. Finally, CacGAS and CicGAS decreased CiRIG-I-mediated the cellular antiviral response and facilitated viral replication. Taken together, data in this study identify CacGAS and CicGAS as negative regulators in RIG-I-like receptor signaling, which extends the current knowledge regarding the role of fish cGAS in the innate antiviral response.
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Proteínas de Peixes/genética , Interferon Tipo I/metabolismo , Nucleotidiltransferases/genética , Infecções por Rhabdoviridae/imunologia , Rhabdoviridae/fisiologia , Animais , Carpas , Cyprinidae , Proteínas de Peixes/imunologia , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica , Carpa Dourada , Células HEK293 , Humanos , Imunidade Inata/genética , Nucleotidiltransferases/imunologia , Nucleotidiltransferases/metabolismo , Transdução de Sinais , Ubiquitinação , Proteínas de Peixe-Zebra/genéticaRESUMO
Fish IFN regulatory factor 3 (IRF3) is a crucial transcription factor in the IFN activation signaling pathway, which leads to IFN production and a positive cycle. Unrestricted IFN expression results in hyperimmune responses and therefore, IFN must be tightly regulated. In the current study, we found that zebrafish Ub-activating enzyme (Uba1) negatively regulated IRF3 via the K-48 ubiquitin proteasome degradation of IRF3. First, ifn expression stimulated by spring viraemia of carp virus infection was blunted by the overexpression of Uba1 and enhanced by Uba1 knockdown. Afterward, we found that Uba1 was localized in the cytoplasm, where it interacted with and degraded IRF3. Functional domains analysis revealed that the C-terminal ubiquitin-fold domain was necessary for IRF3 degradation by Uba1 and the N-terminal DNA-binding domain of IRF3 was indispensable for the degradation by Uba1.The degradation of IRF3 was subsequently impaired by treatment with MG132, a ubiquitin proteasome inhibitor. Further mechanism analysis revealed that Uba1 induced the K48-linked Ub-proteasomal degradation of IRF3. Finally, the antiviral capacity of IRF3 was significantly attenuated by Uba1. Taken together, our study reveals that zebrafish Uba1 interacts with and activates the ubiquitinated degradation of IRF3, providing evidence of the IFN immune balance mechanism in fish.
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Fator Regulador 3 de Interferon/metabolismo , Interferon beta/metabolismo , Ubiquitinação/fisiologia , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Antivirais/metabolismo , Linhagem Celular , Células HEK293 , Humanos , Ligação Proteica/fisiologia , Proteólise , Transdução de Sinais/fisiologia , Ubiquitina/imunologiaRESUMO
Fish interferon (IFN) is a crucial cytokine for a host to resist external pathogens, conferring cells with antiviral capacity. Meanwhile, grass carp reovirus (GCRV) is a strong pathogen that causes high mortality in grass carp. Therefore, it is necessary to study the strategy used by GCRV to evade the cellular IFN response. In this study, we found that GCRV 35-kDa protein (VP35) inhibited the host IFN production by degrading mitochondrial antiviral signaling (MAVS) protein through the autophagy pathway. First, the overexpression of VP35 inhibited the IFN activation induced by polyinosinic-polycytidylic acid (poly I:C) and MAVS, and the expression of downstream IFN-stimulated genes (ISGs) was also decreased by using VP35 under the stimulation. Second, VP35 interacted with MAVS; the experiments of truncated mutants of MAVS demonstrated that the caspase recruitment domain (CARD) and proline-rich (PRO) domains of MAVS were not necessary for this binding. Then, MAVS was degraded by using VP35 in a dose-dependent manner, and 3-MA (the autophagy pathway inhibitor) significantly blocked the degradation, meaning that MAVS was degraded by using VP35 in the autophagy pathway. The result of MAVS degradation suggested that the antiviral capacity of MAVS was remarkably depressed when interrupted by VP35. Finally, in the host cells, VP35 reduced ifn transcription and made the cells vulnerable to virus infection. In conclusion, our results reveal that GCRV VP35 impairs the host IFN response by degrading MAVS through the autophagy pathway, supplying evidence of a fish virus immune evasion strategy.