RESUMEN
AIMS: Growth differentiation factor 15 (GDF15) plays an important role in multiple inflammatory disorders. We aimed to analyze serum GDF15 levels in adult patients with idiopathic inflammatory myopathies (IIMs). METHODS: Serum GDF15 levels were measured in 179 adult patients with IIMs and 76 healthy controls (HCs). The association between GDF15 levels and disease variables was analyzed using Spearman's rank correlation. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminatory ability of GDF15 and the GDF15-to-lymphocyte ratio (GLR). Machine learning methods were applied to build predictive models. RESULTS: GDF15 levels and GLR were significantly elevated in patients with adult IIMs than in HCs. Compared with patients in remission, both GDF15 and GLR were significantly higher in myositis patients in an active phase. GDF15 levels correlated positively with myositis disease activity indices and negatively correlated with lymphocyte and platelet counts. ROC curve analysis revealed that GDF15 levels and GLR outperformed muscle enzymes and distinguished well between patients with active disease and those in remission. Furthermore, even in the normal muscle enzyme group, GDF15 levels and GLR were also well-distinguished between patients with active disease and those in remission. Using machine learning, a logistic regression model of GDF15 combined with creatine kinase and lymphocyte count was constructed and had a reliable predictive value for disease activity. CONCLUSIONS: GDF15, particularly GLR, was significantly correlated with disease activity in adult patients with IIMs. They could serve as useful biochemical markers for evaluating disease activity, monitoring disease progression, and guiding treatment in adult patients with IIMs.
RESUMEN
Prostaglandin-endoperoxide synthase 2 (PTGS2), a common biological macromolecule, is pivotal for innate immunity and pathogen recognition. In this study, we identified and characterized a CcPTGS2a-like gene in the common carp (Cyprinus carpio) with an open reading frame (ORF) of 1821 bp and epidermal growth factor and peroxidase domains. Our multiple sequence analysis revealed high homology between the amino acid sequence of CcPTGS2a-like and those of its homologs in other fish. CcPTGS2a-like mRNA and protein expressions were significantly upregulated in the spleen, head kidney, liver, and gill tissues upon exposure to Aeromonas hydrophila stimulation. CcPTGS2a-like protein recognized the conserved bacterial surface components and exhibited detectable bacterial binding activity. CcPTGS2a-like overexpression before exposure to A. hydrophila notably enhanced the survival rate of common carp, concomitant with decreased bacterial burden. The NF-κB/ERK signaling pathway initiated the immune response in common carp upon infection with A. hydrophila. CcPTGS2a-like overexpression or interference in the head kidney and Epithelioma papulosum cyprinid cells could modulate the p-NF-κB (p-p-65), p-IκBα, and p-ERK1/2 levels as well as the IL-1ß and IL-6 mRNA expression. These results indicated potential CcPTGS2a-like involvement in the immune response of the common carp to bacterial infections through the NF-κB/ERK signaling pathway.
Asunto(s)
Aeromonas hydrophila , Carpas , Enfermedades de los Peces , Proteínas de Peces , Regulación de la Expresión Génica , Infecciones por Bacterias Gramnegativas , Inmunidad Innata , FN-kappa B , Animales , Carpas/inmunología , Carpas/genética , Aeromonas hydrophila/fisiología , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Proteínas de Peces/química , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Enfermedades de los Peces/inmunología , FN-kappa B/genética , FN-kappa B/metabolismo , FN-kappa B/inmunología , Inmunidad Innata/genética , Regulación de la Expresión Génica/inmunología , Secuencia de Aminoácidos , Filogenia , Alineación de Secuencia/veterinaria , Perfilación de la Expresión Génica/veterinaria , Transducción de Señal , Sistema de Señalización de MAP Quinasas/inmunología , Secuencia de BasesRESUMEN
Sequestosome 1 (SQSTM1/p62) is a selective autophagy adapter protein that participates in antiviral and bacterial immune responses and plays an important regulatory role in clearing the proteins to be degraded and maintaining intracellular protein homeostasis. In this study, two p62 genes were cloned from common carp (Cyprinus carpio), namely Ccp62-1 and Ccp62-2, and conducted bioinformatics analysis on them. The results showed that Ccp62s had the same structural domain (Phox and Bem1 domain, ZZ-type zinc finger domain, and ubiquitin-associated domain) as p62 from other species. Ccp62s were widely expressed in various tissues of fish, and highly expressed in immune organs such as gills, spleen, head kidney, etc. Subcellular localization study showed that they were mainly distributed in punctate aggregates in the cytoplasm. After stimulation with Aeromonas hydrophila and spring viraemia of carp virus (SVCV), the expression level of Ccp62s was generally up-regulated. Overexpression of Ccp62s in EPC cells could inhibit SVCV replication. Upon A. hydrophila challenge, the bacterial load in Ccp62s-overexpressing group was significantly reduced, the expression levels of pro-inflammatory cytokines and interferon factors were increased, and the survival rate of the fish was improved. These results indicated that Ccp62s were involved in the immune response of common carp to bacterial and viral infections.
Asunto(s)
Aeromonas hydrophila , Carpas , Enfermedades de los Peces , Proteínas de Peces , Infecciones por Bacterias Gramnegativas , Inmunidad Innata , Filogenia , Infecciones por Rhabdoviridae , Rhabdoviridae , Animales , Carpas/inmunología , Carpas/genética , Enfermedades de los Peces/inmunología , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Aeromonas hydrophila/fisiología , Inmunidad Innata/genética , Rhabdoviridae/fisiología , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Rhabdoviridae/inmunología , Infecciones por Rhabdoviridae/veterinaria , Regulación de la Expresión Génica/inmunología , Proteína Sequestosoma-1/genética , Proteína Sequestosoma-1/inmunología , Perfilación de la Expresión Génica/veterinaria , Alineación de Secuencia/veterinaria , Secuencia de Aminoácidos , Autofagia/inmunologíaRESUMEN
Increased rates of indeterminate QuantiFERON-TB Gold In-Tube (QFT-GIT) results have been reported since the COVID-19 epidemic in Hunan Province, China. The indeterminate result (ITR) rate of QFT increased from an average of 5.2% to 12.4%, paralleling the first COVID-19 pandemic wave in the region. QFT-GIT results of 243 hospitalized patients with COVID-19 from January 2022 to April 2023 at Xiangya Hospital of Central South University were analyzed. Of the 243 patients, 71 (29.2%) had ITRs due to reduced interferon-gamma production in the positive control. Multiple factors are associated with ITRs, such as disease severity, respiratory failure incidence, immunosuppressant use, and prognosis. Additionally, interferon-gamma (Mitogen-Nil) levels differed significantly depending upon disease severity, prognosis, immunosuppressant use, sepsis symptoms, respiratory failure, or hyperlipidemia. An abnormal increase in the ITR rate in the QFT was observed after the COVID-19 pandemic, and an optimal machine learning predictive model for indeterminate QFT results was established.
Asunto(s)
COVID-19 , Tuberculosis Latente , Insuficiencia Respiratoria , Tuberculosis , Humanos , Tuberculosis/diagnóstico , Ensayos de Liberación de Interferón gamma/métodos , Interferón gamma , Pandemias , Inmunosupresores/uso terapéutico , China/epidemiología , Prueba de Tuberculina/métodos , Tuberculosis Latente/diagnósticoRESUMEN
OBJECTIVE: To analyze the predictive effect of a back propagation (BP) neural network, random forest (RF) and decision tree model on the prognosis of elderly patients with cardiogenic shock after extracorporeal membrane oxygenation (ECMO). METHODS: This is a retrospective analysis of the clinical data of elderly patients with cardiogenic shock (258 cases) who underwent ECMO in People's Hospital of Guangxi Zhuang Autonomous Region from January 2016 to January 2022. All patients were followed up for 6 months after ECMO treatment. The prognosis was evaluated, and the prognostic factors were analyzed. BP neural network, RF and decision tree were used to establish predictive models, and the predictive performance of the models was evaluated. RESULTS: Among the 258 elderly patients with cardiogenic shock, 52 (20.16%) died 6 months after the ECMO treatment. Based on BP neural network, RF, and decision tree, predictive models for the prognosis and death of elderly patients with cardiogenic shock were constructed. A test set was used to predict the performance of the three models. The results showed that the predictive performances of the three models were all more than 80.00%. The accuracy, sensitivity, and specificity of the RF model were 0.987, 1.000, and 0.929 respectively, which were higher than those of the decision tree model. The area under the receiver operating characteristic curve (AUC) of the RF model was 1.000, which was higher than 0.916 for the decision tree model. DeLong test showed that there was a significant difference in the AUC of the RF model compared to the decision tree test set (D=-2.063, P=0.042 < 0.05). CONCLUSION: The predictive performance is good in all the three models, which have a high application value for prognosis of ECMO in elderly patients with cardiogenic shock. In clinical practice, predictive models should be selected according to the actual situation, so clinicians and patients can make decisions.
RESUMEN
Purpose: The present study aimed to identify the characteristics, predictors, and imaging features of poor recovery in cases of cerebral venous sinus thrombosis (CVST). Patients and Methods: A total of 290 consecutive adult patients with CVST were enrolled from January 2017 to December 2021 from five hospitals in Nanning, Guangxi. According to the modified Rankin scale (mRS) score at hospital discharge, the patients were classified into good prognosis (GP, mRS ≤2) groups and poor prognosis (PP, mRS>2) groups. Logistic regression was used to identify factors associated with clinical outcomes. Results: Of the 290 patients, 35 were assigned to the PP group and 255 to the GP group. No significant difference in sex was observed between the two groups. Headache (76.21%) was the most frequent symptom of CVST, and local head and neck infection was the major comorbidity (26.21%). Approximately half of the patients (48.62%) had brain injury lesions <1 cm, and the most commonly affected sinus was the lateral sinus (81.03%). Less-common headaches (odds ratio [OR]: 2.769, p=0.046), altered mental status (OR: 0.122, p<0.001), hematologic disorder (OR: 0.191, p=0.045), and injury to multiple lobes (OR: 0.166, p=0.041) were associated with poor clinical outcomes. Conclusion: Headache was the most common and protective manifestation of CVST, and disturbances in consciousness were an important indication of poor clinical prognosis. Patients with hematologic diseases also tended to have poor outcomes. No significant correlation was found between the number and location of venous sinus thromboses and clinical prognosis; however, intracranial injury involving multiple lobes was often associated with poor prognosis.
RESUMEN
(1) Background: Minimal hepatic encephalopathy (MHE) is an important complication of decompensated cirrhosis. Previous studies have demonstrated spontaneous brain activity alterations in cirrhotic patients with MHE. However, the reported results are inconsistent, which has limited our understanding of the potential neural mechanisms. Thus, we conducted a quantitative meta-analysis of resting-state functional imaging studies to identify the regional activity alterations consistently involved in MHE. (2) Methods: We searched six databases to include resting-state functional imaging studies and compared spontaneous brain activity patterns between MHE patients and healthy controls (HCs), and between cirrhotic patients without minimal hepatic encephalopathy (NMHE) and HCs. Then, a separate whole-brain voxel-wise meta-analysis between MHE or NMHE patients and HCs was conducted using seed-based d mapping with permutation of subject images. We further conducted the conjunction analysis to assess the distinct regional activity alterations between MHE and NMHE patients as compared to HCs. (3) Results: Thirteen studies with twenty datasets were included in this meta-analysis. Compared with HCs, MHE patients showed decreased spontaneous brain activity in the left superior frontal gyrus, left median cingulate/paracingulate gyri, and right precuneus. Compared with NMHE patients, MHE patients indicated decreased spontaneous brain activity in the left superior frontal gyrus, left median cingulate/paracingulate gyri, and right precuneus. (4) Conclusions: MHE is associated with spontaneous brain activity alterations involving the left superior frontal gyrus and median cingulate/paracingulate gyri, which may implicate primarily in spatial working memory and emotional disorders. These findings may contribute to a better understanding of the potential neural mechanisms, and guide further research.
RESUMEN
To elucidate the luminescence mechanism of highly efficient blue Cu(N^N)(POP)+-type thermally activated delayed fluorescence (TADF) materials, we have selected Cu(pytfmpz)(POP)+ (1) and Cu(pympz)(POP)+ (2) as targets to investigate the photophysical properties in both solution and solid phases. The self-consistent electrostatic potential (ESP) embedded charge within the quantum mechanics/molecular mechanics (QM/MM) method demonstrates a greater advantage over the charge equilibrium (QEQ) in accurately calculating atomic charges and reasonably describing the polarization effect, ultimately resulting in a favorable consistency between simulation and experimental measurements. After systematic and quantitative simulation, it has been found that complex 2, with an electron-donating group of -CH3, exhibits a much more blue-shifted spectrum and a significantly enhanced efficiency in comparison to complex 1 with -CF3. This is due to the widened HOMO-LUMO gap as well as the narrowed energy gap between the lowest singlet and triplet excited states (ΔEST), respectively. Then, the designed complex 3 is introduced with a stronger electron donor and larger tert-butyl group, which plays a key role in simultaneously suppressing the structural distortion and reducing the ΔEST. This leads to a faster reverse intersystem crossing process than that of the two experimental complexes in solution, turning out to be a new deep-blue-emitting material with excellent TADF performance.
RESUMEN
Although Poly C Binding Protein 1 (PCBP1) affects cellular ferroptosis and mitochondrial dysfunction, the mechanisms by which PCBP1 regulates bladder cancer (BC) cell functions are unknown. In this study, two BC cell lines (T24 and UMUC3) were treated with different doses of ferroptosis inducer erastin to analyze the effect of PCBP1. Online databases (RPISeq and CatRAPID) were used to predict the possible direct interaction between PCBP1 protein and serine ß-lactamase-like protein (LACTB) mRNA, which was further validated via RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays. Mitochondria injury and ferroptosis were evaluated using CCK-8 assay, TUNEL staining, flow cytometry, corresponding kits, and JC-1 staining. In vivo experiments were conducted using tumor xenograft models. Quantitative reverse-transcription polymerase chain reaction was used to detect transcript expression levels, while protein levels were analyzed using western blot and immunohistochemistry. PCBP1 expression was significantly upregulated in BC tissues and cell lines. Also, PCBP1 knockdown increased erastin-mediated ferroptosis in T24 and UMUC3 cells, while PCBP1 overexpression decreased erastin-mediated ferroptosis in T24 and UMUC3 cells. Mechanistic results showed that LACTB mRNA is a novel PCBP1-binding transcript. LACTB upregulation promoted erastin-induced ferroptosis and mitochondrial dysfunction. Furthermore, LACTB overexpression reversed PCBP1-mediated ferroptosis protection, including decreased ROS and enhanced mitochondrial function, which were further alleviated after phosphatidylserine decarboxylase (PISD) overexpression. Moreover, PCBP1 silencing significantly enhanced tumor inhibition effect of sulfasalazine in xenograft mice transplanted with T24 and UMUC3 cells, leading to LACTB upregulation and PISD downregulation. In conclusion, PCBP1 protects BC cells against mitochondria injury and ferroptosis via LACTB/PISD axis.
Asunto(s)
Ferroptosis , Neoplasias de la Vejiga Urinaria , Humanos , Animales , Ratones , Neoplasias de la Vejiga Urinaria/genética , Mitocondrias , ARN , ARN Mensajero/genética , Estabilidad del ARN , Proteínas de Unión al ADN , Proteínas de Unión al ARN/genética , beta-Lactamasas/farmacología , Proteínas de la Membrana , Proteínas MitocondrialesRESUMEN
Growth differentiation factor 15 (GDF15) is a pleiotropic cytokine, which is involved in the cellular stress response following acute damage. However, the functional role of GDF15 in triple-negative breast cancer (TNBC) has not been fully elucidated. ELISA, Western blot, and PCR assays as well as bioinformatics analyses were conducted to observe the expression of GDF15. Cell Counting Kit-8, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet staining assays were conducted to evaluate paclitaxel resistance and cell viability. Cell apoptosis was analyzed by Western blotting. Murine xenograft model assay was employed to evaluate tumor growth in vivo . Our data indicate that GDF15 is markedly elevated in paclitaxel-resistant TNBC cells, which is significantly associated with unfavorable prognosis. Silencing of GDF15 robustly inhibits the proliferation of tumor cells and increases their sensitivity to paclitaxel in vitro and in vivo , whereas the treatment of purified GDF15 protein confers breast cancer cells with chemoresistance ability. Moreover, GDF15 activates protein kinase B (AKT) /mammalian target of rapamycin (mTOR) signaling, inhibition of AKT or mTOR reverses the prosurvival effect of GDF15 and enhances the antitumor efficacy of paclitaxel in TNBC cells. Altogether, our study uncovers the role of GDF15 in tumor growth and paclitaxel resistance, implicating a potential therapeutic target for TNBC.
Asunto(s)
Proteínas Proto-Oncogénicas c-akt , Neoplasias de la Mama Triple Negativas , Animales , Humanos , Ratones , Línea Celular Tumoral , Proliferación Celular , Resistencia a Antineoplásicos , Factor 15 de Diferenciación de Crecimiento/metabolismo , Factor 15 de Diferenciación de Crecimiento/farmacología , Factor 15 de Diferenciación de Crecimiento/uso terapéutico , Mamíferos/metabolismo , Paclitaxel/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
BACKGROUND: The effectiveness of endovascular treatment (EVT) in patients with mild stroke (National Institutes of Health Stroke Scale score ≤5) and acute anterior circulation large vessel occlusion (AACLVO) remains unknown. OBJECTIVE: To conduct a meta-analysis to compare the efficacy and safety of EVT in patients with mild stroke and AACLVO. METHODS: EMBASE, Cochrane Library, PubMed, and Clinicaltrials.gov databases were searched until October 2022. Both retrospective and prospective studies which compared the clinical outcomes between EVT and medical treatment were included. ORs and 95% confidence intervals (CIs) for excellent and favorable functional outcomes, symptomatic intracranial hemorrhage (ICH), and mortality were pooled using a random-effects model. A propensity score (PS)-based methods adjusted analysis was also performed. RESULTS: 4335 patients from 14 studies were included. In patients with mild stroke and AACLVO, EVT presented no marked differences in excellent and favorable functional outcomes and mortality compared with medical treatment. A higher risk of symptomatic ICH (OR=2.79; 95% CI 1.49 to 5.24; P=0.001) was observed with EVT. Subgroup analysis revealed that EVT had potential benefit for proximal occlusions with excellent functional outcomes (OR=1.68; 95% CI 1.01 to 2.82; P=0.05). Similar results were observed when PS-based methods adjusted analysis was used. CONCLUSION: EVT did not significantly benefit clinical functional outcomes in comparison with medical treatment in patients with mild stroke and AACLVO. However, it may improve functional outcomes when treating patients with proximal occlusion, despite being associated with an increased risk of symptomatic ICH. Stronger evidence from ongoing randomized controlled trials is required.
Asunto(s)
Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular , Humanos , Isquemia Encefálica/terapia , Estudios Retrospectivos , Estudios Prospectivos , Trombectomía/métodos , Resultado del Tratamiento , Procedimientos Endovasculares/métodos , Accidente Cerebrovascular/cirugía , Hemorragias Intracraneales/etiologíaRESUMEN
Objective: Ischemic stroke is a common complication in patients with tubercular meningitis (TBM). However, the risk factors for Ischemic stroke in TBM patients are not fully understood, especially in those patients without conventional vascular risk factors. The aim of the present study was to explore the clinical features and independent risk factors for tubercular meningitis-related Ischemic stroke (TBMRIS). Methods: Tubercular meningitis patients with acute Ischemic stroke without conventional vascular risk factors were recruited between July 2010 and July 2020 as the TBMRIS group. Patients who solely had tubercular meningitis were recruited as the control group (TMB group). Demographic characteristics, clinical presentations, and cerebrospinal fluid (CSF) examinations were collected, and multiple logistic regression analysis was applied to analyse the independent risk factors for TBMRIS. Results: A total of 70 TBMRIS patients and 70 TMB patients were enrolled. Most (82.86%) of the TBMRIS patients experienced Ischemic stroke events within 3 months after the diagnosis of tubercular meningitis. The multiple logistic regression analysis revealed that variation in red blood cell distribution width (RDW-CV), mean platelet volume (MVP), C-reactive protein (CRP), CSF glucose and Modified Research Council Grade II (MRC Grade II) were independent risk factors for TBRIS. The AUC of the identification model was 0.808, with a sensitivity of 68.60% and a specificity of 84.30%. Conclusion: This study revealed that RDW-CV, MVP, CRP, CSF glucose and MRC Grade II are potential independent risk factors for TBMRIS. The identification model established in this study may help monitor TBM patients who are at high risk of developing TBMRIS.
RESUMEN
Objective: Hepatocellular carcinoma (HCC) is the sixth most commonly occurring cancer and ranks third in mortality among all malignant tumors; as a result, HCC represents a major human health issue. Although aberrant glycosylation is clearly implicated in HCC, changes in serum immunoglobulin (Ig)G and IgM glycosylation have not been comprehensively characterized. In this study, we used lectin microarrays to evaluate differences in serum IgG and IgM glycosylation among patients with HCC, hepatitis B cirrhosis (HBC), or chronic hepatitis B (CHB), and healthy normal controls (NC) and aimed to establish a model to improve the diagnostic accuracy of HCC. Methods: In total, 207 serum samples collected in 2019-2020 were used for lectin microarray analyses, including 97 cases of HCC, 50 cases of HBC, 30 cases of CHB, and 30 cases of NC. Samples were randomly divided into training and validation groups at a 2:1 ratio. Training group data were used to investigate the diagnostic value of the relative signal intensity for the lectin probe combined with alpha-fetoprotein (AFP). The efficacy of models for HCC diagnosis were analyzed by receiver operating characteristic (ROC) curves. Results: In terms of IgG, a model combining three lectins and AFP had good diagnostic accuracy for HCC. The area under the ROC curve was 0.96 (P < 0.05), the sensitivity was 82.54%, and the specificity was 100%. In terms of IgM, a model including one lectin combined with AFP had an area under the curve of 0.90 (P < 0.05), sensitivity of 75.41%, and specificity of 100%. Conclusion: Estimation of serum IgG and IgM glycosylation could act as complementary techniques to improve diagnosis and shed light on the occurrence and development of the HCC.
Asunto(s)
Carcinoma Hepatocelular , Hepatitis B , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , alfa-Fetoproteínas , Neoplasias Hepáticas/patología , Lectinas , Biomarcadores de Tumor , Cirrosis Hepática , Inmunoglobulina M , Inmunoglobulina GRESUMEN
Background: Intercellular communication mediated by ligand-receptor interactions in tumor microenvironment (TME) has a profound impact on tumor progression. This study aimed to explore the molecular subtypes mediated by ligand-receptor (LR) pairs in triple negative breast cancer (TNBC), identify the most important LR pairs to construct a prognostic risk model, and study their effect on TNBC immunotherapy. Methods: LR pairs subclasses of TNBC were categorized by consensus clustering based on LR Pairs in METABRIC dataset. Least absolute shrinkage and selection operator (LASSO) Cox regression and stepwise Akaike information criterion (stepAIC) were conducted to build a LR pairs score model. The relationship between LR pairs score and immune cell infiltration, stromal score and immune score associated with TME was analyzed, and the prediction of drug therapy and immunotherapy efficacy by LR pairs score was evaluated. Results: According to the expression pattern of 145 TNBC prognostic LR pairs, the samples were divided into three subclasses with different survival outcomes, copy number variation (CNV), TME immune cell infiltration, stromal score and immune score. The LR pairs score model constructed in the METABRIC dataset was composed of four LR pairs, and its predictive significance for TNBC prognosis was verified in GSE58812 and GSE21653 cohorts. In addition, LR pairs score was negatively correlated with several immune pathways regulating immunity and immune score, and related to the sensitivity of anti-neoplastic drugs and the effect of anti-PD-L1 therapy. Conclusion: Our study confirmed the impact of LR pairs on the molecular heterogeneity of TNBC, characterized three LR pairs subtypes with different survival outcomes and TME patterns, and proposed a LR pairs score system with predictive significance for TNBC prognosis and anti-PD-L1 therapeutic effect, which provides a potential evaluation scheme for TNBC management.
Asunto(s)
Neoplasias de la Mama Triple Negativas , Variaciones en el Número de Copia de ADN , Humanos , Ligandos , Pronóstico , Neoplasias de la Mama Triple Negativas/metabolismo , Microambiente TumoralRESUMEN
Objective: There have been only a few studies of ischemic stroke in patients with pulmonary tuberculosis (pTB). This study aimed to explore the clinical features and the underlying pathogenesis of pulmonary tuberculosis-related ischemic stroke (TBRIS). Methods: Active pulmonary tuberculosis patients with acute ischemic stroke (without conventional vascular risk factors) were recruited as the TBRIS group. Patients who solely had active pulmonary tuberculosis were recruited as the control group (pTB group). Clinical data were collected, and multiple logistic regression analysis was applied to analyze the independent risk factors for TBRIS. Results: A total of 179 TBRIS patients and 179 pTB patients were enrolled. Most (56.42%) of the TBRIS patients experienced the ischemic stroke events within 3 months after the diagnosis of tuberculosis. The multiple logistic regression analysis revealed that an increased mean platelet volume; elevated plasma D-dimer, C-reactive protein, and serum ferritin levels; and an increased monocyte percentage were independent risk factors for TBRIS. The AUC of the identification model was 0.778, with a sensitivity of 70.30% and a specificity of 78.90%. Conclusion: The findings in the present study suggested that most of the TBRIS patients experienced ischemic stroke within 3 months after the diagnosis of tuberculosis. And the more intensive immune response to the tuberculosis infection in the TBRIS group contributed to the initiation of platelet activation and to the development of a hypercoagulable state, which were attributed to the pathogenesis of TBRIS. Index of TBRIS equaling to 0.3234 facilitates clinicians to identify the pTB patients who were at higher risk for TBRIS, and allow physicians to take further effective measures to prevent ischemic stroke in patients with pTB. However, our findings will need to be confirmed by further studies.
RESUMEN
BACKGROUND: The features of indeterminate results (ITRs) due to high interferon gamma (IFN-γ > 8.0 IU/mL) concentrations in Nil tubes of QuantiFERON-TB Gold in-Tube (QFT-GIT) have not been well studied. Therefore, this study aimed at investigating the features of ITRs and optimization alternatives for this method. METHODS: We used the plasma exchange method to reduce the ITR rate due to high Nil concentrations (Nil > 8.0 IU/mL) between March 2020 and September 2021 at Xiangya Hospital of Central South University in China. One hundred and eleven out of 28,193 patient samples were considered ITRs due to Nil > 8.0 IU/mL. Of these 111, blood was re-sampled from 82 patients (pretreated group) who received the plasma exchange. Moreover, 40 out of 82 (blood volume ≥ 5 mL) received pretreated QFT-GIT and standard QFT-GIT (untreated group) simultaneously, while the remaining 42 received pretreated QFT-GIT only. The statistical difference between groups was evaluated. Cohen's kappa coefficient was used to assess the level of agreement between the pretreated and untreated group. RESULTS: Of the 28,193 subjects, 1,083 (3.8%) had ITRs, and 111 (0.4%) had ITRs due to Nil > 8.0 IU/mL. The population studied had a mean age of 52.9 years, and 70.3% were men, which is a larger proportion than that in patients with ITR and the overall population. Significantly decreased IFN-γ levels in Nil tubes were detected using the pretreated QFT-GIT compared with standard QFT-GIT (p < 0.01). The determinate results rate in the pretreated group was significantly higher than that of the untreated group (80% (32/40) vs 57.5%, (23/40), p = 0.03). Further comparison revealed that the pretreated group was consistent with the untreated group in 17/20 (85%) positive tests, 3/3 (100%) negative tests, and 6/17 (35.3%) ITRs. The overall agreement rate was 26/40 (65%) among all 40 subjects, and the κ value was 0.39 (minimal agreement). The majority of results obtained after pretreatment were positive (71.2%, 59/82) and the agreement rate between clinical diagnosis and pretreated QFT-GIT was at least 61.0% (39/59). CONCLUSION: Plasma exchange pretreated QFT-GIT yields more reliable results than untreated QFT-GIT when processing high Nil concentrations.
Asunto(s)
Ensayos de Liberación de Interferón gamma , Interferón gamma , China , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The difficulty of atmospheric correction based on a radiative transfer model lies in the acquisition of synchronized atmospheric parameters, especially the aerosol optical depth (AOD). At the moment, there is no fully automatic and high-efficiency atmospheric correction method to make full use of the advantages of geostationary meteorological satellites in large-scale and efficient atmospheric monitoring. Therefore, a QUantitative and Automatic Atmospheric Correction (QUAAC) method is proposed which can efficiently correct high-spatial-resolution (HSR) satellite images. QUAAC uses the atmospheric aerosol products of geostationary satellites to match the synchronized AOD according to the temporal and spatial information of HSR satellite images. This method solves the problem that the AOD is difficult to obtain or the accuracy is not high enough to meet the demand of atmospheric correction. By using the obtained atmospheric parameters, atmospheric correction is performed to obtain the surface reflectance (SR). The whole process can achieve fully automatic operation without manual intervention. After QUAAC applied to Gaofen-2 (GF-2) HSR satellite and Himawari-8 (H-8) geostationary satellite, the results show that the effect of QUAAC correction is slightly better than that of the Fast Line-of-sight Atmospheric Analysis of Spectral Hypercubes (FLAASH) correction, and the QUAAC-corrected surface spectral curves have good coherence to that of the synchronously measured by field experiments.
RESUMEN
Two new N-acetyl-á´ -glucosamine derivatives, penichryfurans A (1) and B (2), were obtained from the fermentation of an endophytic fungus Penicillium chrysogenum which inhabited the marine medical red alga Grateloupia turuturu. Their structures were established by detailed spectroscopic analysis of 1D and 2D NMR in combination with HRESIMS data. The absolute configurations were determined by the (Mo2(OAc)4)-induced CD and comparison of the calculated and experimental electronic curcular dichroism (ECD) spectra. Both compounds were evaluated for their in vitro cytotoxic activities against A549, HeLa, and HepG2 cell lines, among which compound 1 exhibited strong cytotoxicity towards the HepG2 cell line with an IC50 value of 9.0 µM.
Asunto(s)
Penicillium chrysogenum , Penicillium , Glucosamina , Células HeLa , Humanos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Penicillium/química , Penicillium chrysogenum/químicaRESUMEN
BACKGROUND: Survival benefit of adjuvant radiotherapy for locally advanced gastric cancer following gastrectomy plus D2 lymphadenectomy has always been controversial. Esophagogastric junction (EGJ) adenocarcinoma, which is usually classified as gastric cancer in East Asia, often has a higher locoregional recurrence rate after operation because of its special anatomical characteristics. The aim of this study is to determine whether adjuvant radiotherapy can improve survival of locally advanced EGJ adenocarcinoma after D2 radical resection. METHODS: In this phase III, randomized, open label, controlled trial, we plan to recruit 378 patients with Siewert type II and III adenocarcinoma of EGJ, who had undergone transabdominal radical surgery and D2 lymphadenectomy, and were divided into pathological stage IIB to IIIC. All patients will be randomized 1:1 to receive either adjuvant chemotherapy alone (control group) or adjuvant chemotherapy plus chemoradiotherapy (experimental group). Patients allocated to control group will receive eight cycles of S-1 plus oxaliplatin (SOX), while the experimental group will receive two cycles of SOX followed by 45-Gy RT combined with S-1 and four additional cycles of SOX. The primary endpoint is 3-year disease-free survival rate (DFS). The secondary endpoints are 3-year overall survival rate (OS), 3-year locoregional recurrence-free survival rate (LRFS), 3-year distant metastasis-free survival rate (DMFS), and quality of life (QoL). DISCUSSION: In the past, the adjuvant treatment of EGJ adenocarcinoma needs to draw on the experience of esophageal adenocarcinoma or gastric adenocarcinoma. In this study, EGJ adenocarcinoma is considered as an independent disease, and the conclusion will provide evidence for optimal adjuvant therapy of locally advanced EGJ adenocarcinoma after D2 radical resection. TRIAL REGISTRATION: ClinicalTrials.gov NCT03973008 . Registered on 1 June 2019 (retrospectively registered), URL: https://clinicaltrials.gov/ct2/show/NCT03973008?term=NCT03973008&draw=2&rank=1.
Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioradioterapia/efectos adversos , Quimioradioterapia Adyuvante/efectos adversos , Quimioterapia Adyuvante , Ensayos Clínicos Fase III como Asunto , Unión Esofagogástrica/patología , Unión Esofagogástrica/cirugía , Humanos , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Oxaliplatino/efectos adversos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugíaRESUMEN
OBJECTIVES: The aim of this study was to estimate the prevalence and antimicrobial susceptibility of Ureaplasma urealyticum and Mycoplasma hominis in a comprehensive teaching hospital Shenyang, China over the past 4 years. METHODS: A total of 1448 individuals with urogenital symptoms underwent mycoplasma testing between April 2016 and March 2020. Detection, identification and antimicrobial susceptibility testing were carried out using Mycoplasma ID/AST kits. RESULTS: The total infection rate of genital mycoplasmas was 37.5% (543/1448 cases) with an observed increase over the past 4 years. The positive rates of all three detected infections, as well as overall infection rate, were significantly higher in females than in males (P < 0.05). A higher positive rate of infection was observed in females aged 25-29 (60.5%), and in the 15-19 years age group (57.7%). The changes observed among all age groups of females were statistically significantly different (P < 0.001). The positive rates of U. urealyticum and M. hominis co-infection among the four seasons during which the survey was carried out were also observed to be statistically different (P = 0.01). More than 70% of U. urealyticum isolates were found to be resistant to ciprofloxacin, and more than 80% of M. hominis isolates were resistant to erythromycin, roxithromycin, azithromycin and clarithromycin. Josamycin, doxycycline and minocycline were most effective against U. urealyticum and M. hominis. CONCLUSIONS: Results of this study found increasing rates of U. urealyticum and M. hominis infection over the past 4 years, particularly among younger age groups. U. urealyticum/Mycoplasma hominis screening among younger age cohorts are therefore strongly recommend to preventing the spread of pathogens. Monitoring antimicrobial resistance is important for preventing transmission of resistant strains of infection and for the management of antibiotics.