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BACKGROUND: Having a gynecological tumor or undergoing treatment can be a traumatic experience for women, as it affects their self-image and sexual relationships and can lead to psychological reactions. Psychological adjustment following cancer occurrence remains a key issue among the survivors. AIM: To examine the current status of quality of life (QoL), anxiety, and depression in patients with gynecological cancer and to analyze the factors associated with it. METHODS: Data for 160 patients with gynecological malignancies treated at Shanxi Bethune Hospital from June 2020 to June 2023 were collected and analyzed retrospectively. Patients' QoL was assessed using the European Organization for Research on Treatment of Cancer Quality of Life Questionnaire Core 30 and the Functional Assessment of Cancer Therapy-General Questionnaire. Their emotional status was evaluated using the Self-Rating Anxiety/Depression Scale. The associated factors of anxiety and depression were analyzed. RESULTS: The overall QoL score of the patients 6 months after surgery was 76.39 ± 3.63 points. This included low levels of social and emotional function and severe fatigue and pain. The scores for physiological, functional, emotional, social, and family well-being exhibited an upward trend following surgery compared with those before surgery. One month after surgery, some patients experienced anxiety and depression, with an incidence of 18.75% and 18.13%, respectively. Logistic analysis revealed that good sleep was a protective factor against anxiety and depression in patients with gynecological tumors, whereas physical pain was a risk factor. CONCLUSION: Patients with gynecological malignancies often experience anxiety and depression. By analyzing the factors that affect patients' QoL, effective nursing measures can be administered.
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Glioblastoma (GBM) tumors are enriched in immune-suppressive myeloid cells and are refractory to immune checkpoint therapy (ICT). Targeting epigenetic pathways to reprogram the functional phenotype of immune-suppressive myeloid cells to overcome resistance to ICT remains unexplored. Single-cell and spatial transcriptomic analyses of human GBM tumors demonstrated high expression of an epigenetic enzyme-histone 3 lysine 27 demethylase (KDM6B)-in intratumoral immune-suppressive myeloid cell subsets. Importantly, myeloid cell-specific Kdm6b deletion enhanced proinflammatory pathways and improved survival in GBM tumor-bearing mice. Mechanistic studies showed that the absence of Kdm6b enhances antigen presentation, interferon response and phagocytosis in myeloid cells by inhibition of mediators of immune suppression including Mafb, Socs3 and Sirpa. Further, pharmacological inhibition of KDM6B mirrored the functional phenotype of Kdm6b-deleted myeloid cells and enhanced anti-PD1 efficacy. This study thus identified KDM6B as an epigenetic regulator of the functional phenotype of myeloid cell subsets and a potential therapeutic target for enhanced response to ICT.
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Glioblastoma , Humanos , Ratones , Animales , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Histona Demetilasas/genética , Perfilación de la Expresión Génica , Fenotipo , Histona Demetilasas con Dominio de Jumonji/genéticaRESUMEN
Increasing evidence shows that immune-related genes (IRGs) play an important role in bariatric surgery (BS). We identified differentially expressed immune-related genes (DEIRGs) of adipose tissue after BS by analysing the two expression profiles of GEO (GSE59034 and GSE29409). Subsequently, enrichment analysis, GSEA and PPI networks were examined to identify the hub IRGs and related pathways. The performance of the signature was evaluated by area under the curve (AUC) of the receiver operating characteristic (ROC). CIBERSORT algorithm was used to evaluate the relative abundance of infiltrated immune cells.42 DEIRGs were found between the GSE59034 and GSE29409 datasets. The AUC of the signature was 0.904 and 0.865 in the GSE58979 and GSE48452, respectively. Interestingly, the signature also showed good performance in diagnosing non-alcoholic fatty liver disease (NAFLD) (AUC was 0.834 and 0.800, respectively). The number of neutrophils, macrophages M2, macrophages M0 and dendritic cells activated decreased significantly. After BS, the infiltration of T cells regulatory, monocytes, mast cells resting and plasma cells in adipose tissue increased. The novel proposed IRGs signature reveals the underlying immune mechanism of BS and is a promising biomarker for distinguishing the severity of NAFLD. This will provide new insights into strategies for treating obesity and NAFLD.
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Cirugía Bariátrica , Enfermedad del Hígado Graso no Alcohólico , Biomarcadores , Perfilación de la Expresión Génica , Humanos , Enfermedad del Hígado Graso no Alcohólico/genética , Curva ROCRESUMEN
Immune checkpoint therapy (ICT) can produce durable antitumor responses in metastatic urothelial carcinoma (mUCC); however, the responses are not universal. Despite multiple approvals of ICT in mUCC, we lack predictive biomarkers to guide patient selection. The identification of biomarkers may require interrogation of both the tumor mutational status and the immune microenvironment. Through multi-platform immuno-genomic analyses of baseline tumor tissues, we identified the mutation of AT-rich interactive domain-containing protein 1A (ARID1A) in tumor cells and expression of immune cytokine CXCL13 in the baseline tumor tissues as two predictors of clinical responses in a discovery cohort (n = 31). Further, reverse translational studies revealed that CXCL13-/- tumor-bearing mice were resistant to ICT, whereas ARID1A knockdown enhanced sensitivity to ICT in a murine model of bladder cancer. Next, we tested the clinical relevance of ARID1A mutation and baseline CXCL13 expression in two independent confirmatory cohorts (CheckMate275 and IMvigor210). We found that ARID1A mutation and expression of CXCL13 in the baseline tumor tissues correlated with improved overall survival (OS) in both confirmatory cohorts (CheckMate275, CXCL13 data, n = 217; ARID1A data, n = 139, and IMvigor210, CXCL13 data, n = 348; ARID1A data, n = 275). We then interrogated CXCL13 expression plus ARID1A mutation as a combination biomarker in predicting response to ICT in CheckMate275 and IMvigor210. Combination of the two biomarkers in baseline tumor tissues suggested improved OS compared to either single biomarker. Cumulatively, this study revealed that the combination of CXCL13 plus ARID1A may improve prediction capability for patients receiving ICT.
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Neoplasias de la Vejiga Urinaria , Animales , Biomarcadores , Biomarcadores de Tumor/genética , Quimiocina CXCL13 , Proteínas de Unión al ADN , Humanos , Ratones , Mutación/genética , Factores de Transcripción/genética , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
The excitation energy transfer (EET) pathways in the sensitization luminescence of EuIII and the excitation energy migration between the different ligands in [Eu(fod)3dpbt] [where fod=6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedione and dpbt=2-(N,N-diethylanilin-4-yl)-4,6-bis(3,5-dimethylpyrazol-1-yl)-1,3,5-triazine], exhibiting well-separated fluorescence excitation and phosphorescence bands of the different ligands, were investigated by using time-resolved luminescence spectroscopy for the first time. The data clearly revealed that upon the excitation of dpbt, the sensitization luminescence of EuIII in [Eu(fod)3dpbt] was dominated by the singlet EET pathway, whereas the triplet EET pathway involving T1(dpbt) was inefficient. The energy migration from T1(dpbt) to T1(fod) in [Eu(fod)3dpbt] was not observed. Moreover, upon the excitation of fod, a singlet EET pathway for the sensitization of EuIII luminescence, including the energy migration from S1(fod) to S1(dpbt) was revealed, in addition to the triplet EET pathway involving T1(fod). Under the excitation of dpbt at 410â nm, [Eu(fod)3dpbt] exhibited an absolute quantum yield for EuIII luminescence of 0.59 at 298â K. This work provides a solid and elegant example for the concept that singlet EET pathway could dominate the sensitization luminescence of EuIII in some complexes.
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Adoptive transfer of tumor-reactive T cells (ACT) has led to modest clinical benefit in the treatment of solid tumors. Failures with this therapy are primarily due to inadequate infiltration and poor function of adoptively transferred cells in the tumor microenvironment. To improve the efficacy of ACT, we combined ACT with dual blockade of CTLA-4 and PD-1. Treatment with anti-CTLA-4 plus anti-PD-1 compared with monotherapy resulted in durable antitumor responses, enhanced effector function of ACT, utilizing PMEL-1 transgenic (Tg+) CD8+ T cells, and improved survival. Using PMEL-1ICOS-/- mice, we showed that deletion of the inducible T-cell costimulator (ICOS) receptor abolished the therapeutic benefits, with selective downregulation of Eomesodermin (Eomes), interferon gamma (IFNγ), and perforin. Higher expression of IFNγ and Eomes was noted in human ICOShi CD8+ T cells compared with ICOSlow counterparts. Together, our data provide direct evidence that ACT combined with immune-checkpoint therapy confers durable antitumor responses, which largely depended on CD8+ T-cell-intrinsic expression of ICOS. Our study provides a foundation of testing combinatorial therapy of ACT of CD8 T cells and dual blocking of CTLA-4 and PD-1 in patients with melanoma.
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Linfocitos T CD8-positivos/inmunología , Antígeno CTLA-4/antagonistas & inhibidores , Inmunoterapia Adoptiva , Proteína Coestimuladora de Linfocitos T Inducibles/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Animales , Antineoplásicos Inmunológicos/uso terapéutico , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/trasplante , Línea Celular Tumoral , Terapia Combinada , Humanos , Proteína Coestimuladora de Linfocitos T Inducibles/genética , Melanoma/inmunología , Melanoma/terapia , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Transducción de SeñalRESUMEN
BACKGROUND: Aspiration pneumonia is a common problem in older people with high mortality and increasing prevalence. OBJECTIVE: The aims of this paper were to systematically review the literature on the antibacterial treatment of aspiration pneumonia in elderly patients and identify the microbiology of aspiration pneumonia. MATERIALS AND METHODS: EMBASE, MEDLINE, and Cochrane databases were systematically searched for studies that examined the clinical efficacy of antibiotic treatment in elderly patients with aspiration pneumonia. Information on study design, antibiotic treatment, study population, participants, microbiology, clinical outcomes, adverse events, and mortality was recorded. RESULTS: There were no definitive clinical trials, placebo-controlled trials, or meta-analyses. Of the eight studies selected for inclusion in the review, the majority utilized and/or compared broad-spectrum antibiotics. No specific antibacterial agent had evidence of superior efficacy. Broad-spectrum antibiotics resulted in the emergence of multiresistant organisms. Anaerobic bacteria were infrequently isolated, suggesting a less important role in the pathogenesis of aspiration pneumonia. CONCLUSION: There is limited evidence with regard to the use of antibiotics in older patients with aspiration pneumonia. Research providing an evidence base for the treatment of aspiration pneumonia in older people is required.
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Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Neumonía por Aspiración/tratamiento farmacológico , Anciano , Antibacterianos/efectos adversos , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/mortalidad , Farmacorresistencia Bacteriana Múltiple , Humanos , Neumonía por Aspiración/microbiología , Neumonía por Aspiración/mortalidad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Enhancer of zeste homolog 2-mediated (EZH2-mediated) epigenetic regulation of T cell differentiation and Treg function has been described previously; however, the role of EZH2 in T cell-mediated antitumor immunity, especially in the context of immune checkpoint therapy, is not understood. Here, we showed that genetic depletion of EZH2 in Tregs (FoxP3creEZH2fl/fl mice) leads to robust antitumor immunity. In addition, pharmacological inhibition of EZH2 in human T cells using CPI-1205 elicited phenotypic and functional alterations of the Tregs and enhanced cytotoxic activity of Teffs. We observed that ipilimumab (anti-CTLA-4) increased EZH2 expression in peripheral T cells from treated patients. We hypothesized that inhibition of EZH2 expression in T cells would increase the effectiveness of anti-CTLA-4 therapy, which we tested in murine models. Collectively, our data demonstrated that modulating EZH2 expression in T cells can improve antitumor responses elicited by anti-CTLA-4 therapy, which provides a strong rationale for a combination trial of CPI-1205 plus ipilimumab.
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Antineoplásicos Inmunológicos/uso terapéutico , Antígeno CTLA-4/antagonistas & inhibidores , Proteína Potenciadora del Homólogo Zeste 2/antagonistas & inhibidores , Ipilimumab/uso terapéutico , Linfocitos T Reguladores/inmunología , Animales , Antineoplásicos Inmunológicos/administración & dosificación , Línea Celular Tumoral , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Inhibidores Enzimáticos/farmacología , Humanos , Indoles/administración & dosificación , Indoles/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Neoplasias Experimentales/enzimología , Neoplasias Experimentales/inmunología , Neoplasias Experimentales/terapia , Piperidinas/administración & dosificación , Piperidinas/farmacología , Linfocitos T Reguladores/efectos de los fármacosRESUMEN
OBJECTIVE: To build an expert system for forensic bones estimation. METHODS: By using the object oriented method, employing statistical data of forensic anthropology, combining the statistical data frame knowledge representation with productions and also using the fuzzy matching and DS evidence theory method. RESULTS: Software for forensic estimation of sex, age and height with opened knowledge base was designed. CONCLUSION: This system is reliable and effective, and it would be a good assistant of the forensic technician.
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Sistemas Especialistas , Antropología Forense/métodos , Medicina Legal/métodos , Diseño de Software , Determinación de la Edad por el Esqueleto/métodos , Algoritmos , Antropometría/métodos , Simulación por Computador , HumanosRESUMEN
Along with the spread of human immunodeficiency virus 1 (HIV-1) infection in the world and the emergence of drug-resistant viral strains, it is urgent to seek the novel potent therapies. Chemokine receptor 5 (CCR5) is one of the main coreceptors involved in the entry of HIV-1 into target cells. Nowadays, a number of CCR5 antagonists have been developed and some of them have progressed to clinical trials or been approved. Research progress has also been made in the CCR5-targeted gene therapy. This review summarizes the recent research progress on the CCR5-targeted drug and gene therapy.
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VIH-1/efectos de los fármacos , Terapia Molecular Dirigida/métodos , Receptores CCR5/metabolismo , Antagonistas de los Receptores CCR5 , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Infecciones por VIH/metabolismo , Infecciones por VIH/patología , Humanos , Receptores CCR5/deficiencia , Receptores CCR5/genéticaRESUMEN
BACKGROUND: Echinococcus granulosus is usually transmitted between canid definitive hosts and ungulate intermediate hosts. METHODOLOGY/PRINCIPAL FINDINGS: Lesions found in the livers of ground squirrels, Spermophilus dauricus/alashanicus, trapped in Ningxia Hui Autonomous Region, an area in China co-endemic for both E. granulosus and E. multilocularis, were subjected to molecular genotyping for Echinococcus spp. DNA. One of the lesions was shown to be caused by E. granulosus and subsequently by histology to contain viable protoscoleces. CONCLUSIONS/SIGNIFICANCE: This is the first report of a natural infection of the ground squirrel with E. granulosus. This does not provide definitive proof of a cycle involving ground squirrels and dogs or foxes, but it is clear that there is active E. granulosus transmission occurring in this area, despite a recent past decline in the dog population in southern Ningxia.